thymosin and Immunologic-Deficiency-Syndromes

Thymosin alpha 1 (Ta1) is a peptide originally isolated from thymic tissue as the compound responsible for restoring immune function to thymectomized mice. Ta1 has a pleiotropic mechanism of action, affecting multiple immune cell subsets that are involved in immune suppression. Ta1 acts through Toll-like receptors in both myeloid and plasmacytoid dendritic cells, leading to activation and stimulation of signaling pathways and initiation of production of immune-related cytokines. Due to the immune stimulating effects of Ta1, the compound would be expected to show utility for treatment of immune suppression, whether related to aging or to diseases such as infection or cancer. Extensive studies in both the preclinical and clinical setting will be summarized in the subsequent sections. These studies have demonstrated improvements in immune system cell subsets and the potential of Ta1 for the treatment of a range of diseases.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; Disease Models, Animal; Humans; Immunity; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Infections; Mice; Neoplasms; Thymalfasin; Thymosin; Vaccines

Links between the nervous and immune systems are suggested by the behavioural conditioning of immunosuppression, the effects of brain lesions and stress on immune responses, and physiological and chemical changes in the brain during immune responses. These links probably include glucocorticoids secreted from the adrenal gland, catecholamines and neuropeptides secreted by sympathetic terminals and the adrenal medulla, certain pituitary hormones, and polypeptides produced by cells of the immune system. The effect of glucocorticoids is not exclusively immunosuppressive, nor is it adequate to explain all the effects of stress. In vitro endogenous opiates facilitate lymphocyte proliferation and natural killer (NK) cell activity, but in vivo opiates appear to inhibit immune responses and impair tumour rejection. Increases of circulating glucocorticoids after infection and an apparent activation of cerebral catecholaminergic cells indicate that challenges to the immune system are interpreted physiologically as stressors. Moreover, they suggest that the brain may be able to monitor the progress of immune responses. Certain protein factors produced by the thymus gland (thymosins) may be able to counter stress-induced deficits in immunological responses.

Topics: Animals; Brain Chemistry; Brain Diseases; Disease Susceptibility; Endorphins; Glucocorticoids; Humans; Immune System; Immunologic Deficiency Syndromes; Mice; Nervous System Physiological Phenomena; Psychoneuroimmunology; Stress, Physiological; Thymosin

Secondary immune deficiency generally involves more profound defects in cellular than humoral immunity. This type of immune deficiency occurs in acquired immunodeficiency syndrome (AIDS), cancer, malnutrition, aging and following immunosuppressive therapy. Immunorestorative therapies were developed for use in the immunotherapy of cancer. Their experimental use in cancer and other diseases such as infections and autoimmunity has demonstrated their safety and their capacity to improve host responses to disease particularly when the host is immunocompromised. Biologicals such as the thymic hormones and interferon have been intensively studied and are briefly reviewed in this paper. Chemically defined drugs such as levamisole, isoprinosine, azimexon, and muramyl dipeptides have also been extensively analyzed and the action of certain purine-related compounds are discussed to exemplify their immunopharmacologic features. The combined uses of biologicals and drugs are suggested to improve the efficiency of immunotherapy.

Topics: Humans; Hypoxanthines; Immunologic Deficiency Syndromes; Immunotherapy; Inosine Pranobex; Interferons; Interleukin-2; Purines; Thymosin; Thymus Extracts; Thymus Hormones; Transfer Factor

The manuscript will provide an in-depth and critical review of the nomenclature, biochemistry, biological properties, and a summary of published and on-going clinical trials with all reported thymic preparations, including both partially purified thymic factors (e.g., thymosin fraction 5, thymostimulin) as well as purified and synthesized thymic peptides (e.g., thymosin alpha 1, thymulin). Particular emphasis will be placed on which thymic peptides should be categorized as true hormones. In addition, the comparative biochemistry and biological activity in animals will be summarized and contrasted for all the currently available thymic factors. The effects, in vitro of thymic factors, on peripheral blood lymphocytes isolated from normal donors and patients with primary immunodeficiency disorders, autoimmune disorders, and neoplastic disorders will also be reviewed. Finally, a detailed critical summary of the clinical trials performed with each of the thymic preparations will be presented with an emphasis on treatment of patients with cancer.

Topics: Amino Acid Sequence; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Autoimmune Diseases; Biological Assay; Cell Differentiation; Epithelium; Humans; Immunologic Deficiency Syndromes; Immunotherapy; Neoplasms; T-Lymphocytes; Terminology as Topic; Thymectomy; Thymic Factor, Circulating; Thymopoietins; Thymosin; Thymus Extracts; Thymus Gland; Thymus Hormones

The epithelial cells of the thymus synthesize at least 30 different polypeptides: the thymic hormones. The structure of 4 of them is well known. They are named thymosin alpha 1, thymopoietin, thymulin and thymic humoral factor. Biological functions and secretion regulation of thymic hormones are described as well as the interactions between brain, thymus and endocrine glands. Blood levels and clinical usefulness of thymic hormones are reviewed in different congenital or acquired immunodeficient states and in autoimmune diseases.

Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Humans; Immunologic Deficiency Syndromes; Peptide Fragments; Thymalfasin; Thymic Factor, Circulating; Thymopentin; Thymopoietins; Thymosin; Thymus Extracts; Thymus Hormones

Topics: Animals; Autoimmune Diseases; Growth Inhibitors; Humans; Immunity; Immunologic Deficiency Syndromes; Interferons; Interleukin-1; Interleukin-2; Lymphotoxin-alpha; Neoplasms; Thymic Factor, Circulating; Thymosin; Thymus Hormones; Transfer Factor

Topics: Animals; Autoimmune Diseases; Dose-Response Relationship, Immunologic; Drug Evaluation; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Immunity; Immunity, Cellular; Immunization; Immunocompetence; Immunologic Deficiency Syndromes; In Vitro Techniques; Molecular Weight; Neoplasms, Experimental; Stimulation, Chemical; Thymosin; Thymus Hormones; Time Factors

Topics: Antibody Formation; Bone Marrow; Bone Marrow Transplantation; Complement System Proteins; Humans; Hypersensitivity, Delayed; Immunoglobulins; Immunologic Deficiency Syndromes; Inflammation; Intestinal Mucosa; Phagocytosis; Skin; Thymosin; Thymus Gland; Transfer Factor

Thymosin fraction 5 contains several distinct hormonal-like factors which are effective in partially or fully inducing and maintaining immune function. Several of the peptide components of fraction 5 have been purified, sequenced and studied in assay systems designed to measure T-cell differentiation and function. These studied indicate that a number of the purified peptides act on different subpopulations of T-cells (see Figure 1). Thymosin beta 3 and beta 4 peptides act on terminal deoxynucleotidyl transferase (TdT) negative precursor T-cells to induce TdT positive cells. Thymosin alpha 1 induces the formation of functional helper cells and conversion of Lyt- cells to Lyt 1+, 2+, 3+ cells. Thymosin alpha 7 induces the formation of functional suppressor T-cells and also converts Lyt- cells to Lyt 1+, 2+, 3+ cells. These studies have provided further evidence that the thymus secretes a family of distinct peptides which act at various sites of the maturation sequence of T-cells to induce and maintain immune function. Phase I and Phase II clinical studied with thymosin in the treatment of primary immunodeficiency diseases, autoimmune diseases, and cancer point to a major role of the endocrine thymus in the maintenance of immune balance and in the treatment of diseases characterized by thymic malfunction. It is becoming increasingly clear that immunological maturation is a process involving a complex number of steps and that a single factor initiating a single cellular event might not be reflected in any meaningful immune reconstitution unless it is the only peptide lacking. Given the complexity of the maturation sequence of T-cells and the increasing numbers of T-cell subpopulations that are being identified, it would be surprising if a single thymic factor could control all of the steps and populations involved. Rather, it would appear that the control of T-cell maturation and function involves a complex number of thymic-specific factors and other molecules that rigidly control the intermediary steps in the differentiation process.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Chemical Phenomena; Chemistry; Humans; Immunologic Deficiency Syndromes; Immunotherapy; Neoplasms; Peptide Fragments; T-Lymphocytes; Thymosin; Thymus Gland; Thymus Hormones

Topics: Ataxia Telangiectasia; B-Lymphocytes; Child; Child, Preschool; Female; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Infant; Lymphocyte Culture Test, Mixed; Pentosyltransferases; Phytohemagglutinins; Purine-Nucleoside Phosphorylase; T-Lymphocytes; Thymosin; Thymus Gland; Uridine

Topics: Amino Acid Sequence; Animals; Humans; Immunity; Immunologic Deficiency Syndromes; Isoelectric Focusing; Mice; Neoplasms; T-Lymphocytes; Terminology as Topic; Thymectomy; Thymosin; Thymus Gland; Thymus Hormones

Topics: Animals; Cattle; Humans; Immunologic Deficiency Syndromes; Mice; Mononuclear Phagocyte System; Neoplasms; Peptides; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: BCG Vaccine; Bone Marrow Transplantation; Humans; Immunologic Deficiency Syndromes; Immunotherapy; Mycobacterium bovis; Neoplasms; Thymosin; Thymus Gland; Transfer Factor; Transplantation, Homologous

Topics: Adenosine Deaminase; Agammaglobulinemia; Bone Marrow Cells; Bone Marrow Transplantation; Cell Differentiation; Chromosome Mapping; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; HLA Antigens; Humans; Immunologic Deficiency Syndromes; Liver Transplantation; T-Lymphocytes; Thymosin; Thymus Gland; Transfer Factor; Transplantation, Homologous; Wiskott-Aldrich Syndrome

Topics: Aging; Animals; Autoimmune Diseases; Disease Models, Animal; Humans; Immunity; Immunologic Deficiency Syndromes; Immunologic Techniques; Leukemia; Neoplasms; T-Lymphocytes; Thymosin; Thymus Gland; Thymus Hormones

Topics: Blood Transfusion; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Child; DiGeorge Syndrome; Female; Fetus; Humans; Immunity, Cellular; Immunoglobulins; Immunologic Deficiency Syndromes; Infant; Male; Plasma; Thymosin; Thymus Gland; Transfer Factor; Transplantation, Homologous

Topics: Aged; Amyloidosis; Animals; Child; DNA; Humans; Immunity; Immunologic Deficiency Syndromes; Immunologic Techniques; Lymphoid Tissue; Mice; Mice, Inbred Strains; Neuromuscular Junction; Pharmacology; RNA; Stimulation, Chemical; T-Lymphocytes; Thymopoietins; Thymosin; Thymus Hormones

Topics: Animals; Animals, Newborn; Autoimmune Diseases; Biological Assay; Cell Differentiation; Female; Graft vs Host Reaction; Histocompatibility Antigens; History of Medicine; Humans; Immunity; Immunologic Deficiency Syndromes; Mice; Mice, Inbred CBA; Mitogens; Neoplasm Transplantation; Pregnancy; T-Lymphocytes; Thymosin; Thymus Extracts; Thymus Gland; Thymus Hormones; Transplantation, Homologous; Transplantation, Isogeneic

Congenitally athymic nude mice (nu/nu) are presented as a model for the study of cell-mediated immunologic deficiencies. These mice possess a vestigial thymus which is incapable of producing mature T-cells as shown by a decreased lymphocyte population carrying the theta antigen and depleted 'thymus-dependent' areas in their peripheral lymphoid organs. However, they have T-cell precursors in their bone marrow. Nude mice lack 'thymosin', a thymic factor secreted by the epithelial cells of the thymus. They also have impaired T-cell functions as demonstrated by an absence of delayed hypersensitivity reactions, an inability to reject skin allografts and a decreased antibody response to some T-dependent antigens. But their response to T-independent antigens is normal. The presence of circulating auto-antibodies and immune-complex type glomerulonephritis in nude mice reinforces the hypothesis that spontaneous autoimmunity and B-cell hyperactivity are associated with T-cell deficiency. On the other hand, they are not especially susceptible to spontaneous tumor development. Correlations are made between the pathologic findings in nude mice and some congenital cellular immunologic disorders in man.

Topics: Agammaglobulinemia; Animals; Antigens; Ataxia Telangiectasia; Autoantibodies; Disease Models, Animal; Graft Rejection; Immunity, Cellular; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Spleen; Syndrome; T-Lymphocytes; Thymosin; Thymus Gland; Wiskott-Aldrich Syndrome

Topics: Adolescent; Adult; Aged; Animals; Arthritis, Rheumatoid; Child; Clinical Trials as Topic; Double-Blind Method; Humans; Immunologic Deficiency Syndromes; Middle Aged; Neoplasms; Rats; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Adjuvants, Immunologic; Clinical Trials as Topic; Humans; Immunologic Deficiency Syndromes; Lung Neoplasms; Thymalfasin; Thymosin; Thymus Hormones

Studies in a variety of animal and human models indicate that thymosin plays a role in the differentiation of a number of T-cell subpopulations. The hypothesis presented is that a normal immune balance depends heavily upon the presence of thymosin-activated suppressor or regulator T-cells. A major thrust in our present research program is to determine whether or not the various disorders discussed here are causally related to abnormal thymosin production by the thymus gland. We are also assessing in animal models the potential value of thymsin in the treatment of specific autoimmune diseases. This information may yield new insights for the management of autoimmune type disorders such as SLE. Results from clinical trials to date suggest that thymosin will have a role in boosting the immune responses of patients with specific thymic malfunctions and may indeed exert an influence via the production of suppressor or regulator T-cells.

Topics: Animals; Autoimmune Diseases; Cell Differentiation; Clinical Trials as Topic; Hodgkin Disease; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Leiomyosarcoma; Leukemia, Lymphoid; Lung Neoplasms; Melanoma; Mice; Multiple Myeloma; T-Lymphocytes; Thymosin; Thymus Extracts

To investigate the immunological function of a yeast expression system for thymosin alpha1 (Talpha1).. A constructed Talpha1 yeast expression system was used to investigate the immunological function of orally administered Talpha1. Dried yeast containing three different concentration of Talpha1 was fed to normal Balb/c mice and other Balb/c mice whose immunities were inhibited in advance by cyclophosphamide. Synthesized Talpha1 peptide was used as positive control and dried yeast with empty plasmid was used as negative control. CD4(+) and CD8(+) levels were detected by flow cytometry assay. TNF-alpha, IFN-gamma, IL-2, IL-6 and IL-10 levels were detected by liquid chip.. In normal Balb/c mice or immune inhibition Balb/c mice, CD8(+) levels were significantly increased. Especially in immune inhibition Balb/c mice, CD8(+) levels in synthesized Talpha1 group (18.77%+/-4.72%), small dose group (13.48%+/-6.17%) and large dose group (22.74%+/-1.09%) were significantly higher than that in empty yeast control group (7.49%+/-2.14%).. Orally administered Talpha1 has its certain immunomodulatory function.

Topics: Administration, Oral; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cyclophosphamide; Cytokines; Immunologic Deficiency Syndromes; Immunologic Factors; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Recombinant Proteins; Saccharomyces cerevisiae; Thymalfasin; Thymosin

Thymosin alpha1 is a biological response modifier that has been used clinically for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracellular mechanisms have been postulated to explain the effect of thymosin alpha1 on hepatocytes infected with hepatitis B virus (HBV). Here, we established a new animal model and the related suitable conditions to access the thymosin activity by means of measuring the production of neutralizing antibody against hepatitis B surface antigen (HBsAg). We proved that chemically synthesized thymosin alpha1 restored the T cell-mediated antibody production following its suppression in mice by 5-fluorouracil (5-FU), and found that thymosin alpha1 showed activity at a low dose of 30 microg/kg. Further studies utilizing the flowcytometric analysis showed that thymosin alpha1 at this dose accelerated the replenishment and maturation of thymocytes while the expression of Smoothened (Smo) of the Hedgehog (Hh)-signaling in CD4-CD8- thymocytes, the potent negative regulator of proliferative responses, was not affected. The restoration of some of the defects in the host defense systems may facilitate elimination of infectious agents, and the present study provides a novel model to define the restoration of T cell-mediated immune responses to hepatitis B virus in vivo.

Topics: Adjuvants, Immunologic; Animals; CD4-CD8 Ratio; Cyclophosphamide; Female; Flow Cytometry; Fluorouracil; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Mice; Mice, Inbred C3H; Organ Size; Stimulation, Chemical; T-Lymphocytes; Thymalfasin; Thymosin; Thymus Gland

In patients with primary immunodeficiencies the role of natural killer (NK)- and lymphokine (IL-2)-activated killer (LAK)-cells is not yet satisfactorily established. Using a clonogenic assay with K562 leukemia target cells, we studied their NK- and LAK-cell activity in vitro. Moreover, the effect of thymosin alpha 1 (T alpha 1) on LAK-cell activity was studied in 11 patients with different immunodeficiencies. The results were compared with data of healthy controls (n = 11) and cord blood samples (n = 6). Common variable immunodeficiency patients demonstrated a mean LAK-cell activity of about 65% of normal controls and cord blood samples. The moderately reduced LAK-cell activity was not affected by T alpha 1. In the immunodeficient other patients, low levels of LAK-cell activity with a mean value of 10% of normal controls were seen. The mean LAK-cell activity could be improved by T alpha 1: three patients showed an improvement of their LAK-cell activity up to 25-30% after T alpha 1 administration in vitro, but in one case T alpha 1 was without any effect. Analysis of the expression of the surface markers CD8, CD16, CD57 and CD8/CD57 revealed that only CD16 positive lymphocytes were significantly less in immunodeficient patients. We found a linear correlation between LAK-cell activity and CD8/CD57 double positive lymphocytes in all patients. Our results demonstrate that suppressed LAK-cell activity from immunodeficient patients can be individually improved by T alpha 1. Further in vivo studies should evaluate thymic peptide immunotherapy for individual immunodeficient patients.

Topics: Adolescent; Adult; Antigens, CD; Child; Fetal Blood; Humans; Immunologic Deficiency Syndromes; Killer Cells, Lymphokine-Activated; Thymalfasin; Thymosin

Immunodeficient ageing (C57BL/10 x DBA/2)F1 mice were treated by a single injection of synthetic thymic hormones and 4 days later their thymus and spleen cells were assayed in vitro for T cell activities. A few nanograms of THF-gamma 2 were found to raise the frequency of mitogen-responsive T cells in thymus and spleen cell populations as well as the frequency of cytokine-producing splenic T cells, up to the levels observed in young mice. Moreover, injection of THF-gamma 2 was found to restore T cell growth factor (TCGF) production by mitogen-stimulated spleen cells. Also, the helper activity of spleen cells was enhanced by this treatment and increased with increasing the THF-gamma 2 dose over a wide range. Similarly, the effects of thymopentin and thymosin-alpha 1 on T helper cell activity increased with increasing the injected dose, but the efficiencies of THF-gamma 2 and thymopentin were, respectively, 400-fold and eight-fold greater than that of thymosin-alpha 1.

Topics: Aging; Amino Acid Sequence; Animals; Cells, Cultured; Female; Immunologic Deficiency Syndromes; Interleukin-2; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Sequence Data; Oligopeptides; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Thymalfasin; Thymopentin; Thymosin; Thymus Hormones

Topics: Adjuvants, Immunologic; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; T-Lymphocytes; Thymosin; Uremia

The untetracontapeptide corresponding to the entire amino acid sequence of deacetylthymosin beta 11 was synthesized by assembling six peptide fragments via the azide followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole in trifluoroacetic acid in the presence of dimethylselenide. The synthetic peptide was tested for its effect on the impaired blastogenic response of phytohemagglutinin-stimulated T-lymphocytes of a uremic patient with common variable immunodeficiency. The synthetic peptide had some restoring activity on the impaired blastogenic response of T-lymphocytes in the one patient tested.

Topics: Amino Acid Sequence; Amino Acids; Fluorometry; Humans; Immunologic Deficiency Syndromes; Male; Molecular Sequence Data; T-Lymphocytes; Thymosin; Uremia

Thymosin fraction 5 polypeptides beta 4 and alpha 1 were tested for their ability to affect certain immunological parameters of human peripheral blood lymphocytes (PBL). PBL were cultured with various concentrations of the peptides for 24 hours. Thymosin beta 4 was found to induce a significant decrease in the expression of the Fc alpha receptors of PBL, as well as in their ability to express antibody dependent cellular cytotoxic (ADCC) activity. In addition, this peptide had the ability to increase the percentage of T4 lymphocytes in normal and immunosuppressed donors and to decrease the percentage of T8 positive cells in normal donors. Finally, beta 4 peptide caused a small increase in the capacity of peripheral blood lymphocytes to form sheep red blood cell (SRBC) rosettes (ER). In parallel experiments thymosin alpha 1 was found inactive. The results presented here indicate that thymosin beta 4 may be used as an immunoregulatory molecule in patients with immunodeficiencies.

Topics: Adjuvants, Immunologic; Antibody-Dependent Cell Cytotoxicity; Humans; Immunologic Deficiency Syndromes; In Vitro Techniques; Lymphocytes; Receptors, Fc; Receptors, IgG; Rosette Formation; T-Lymphocytes; Thymalfasin; Thymosin

A Hispanic infant girl with DiGeorge syndrome underwent successful bone marrow transplantation (BMT) at age 28 1/2 weeks. She had typical facies, a cardiac defect, hypoparathyroidism, severe T and B cell immunodeficiency, and low levels of facteur thymique serique (FTS). In vitro incubation of the peripheral blood lymphocytes with thymosin alpha 1 showed no increase in the number of T cells on two occasions. A fetal thymus for transplantation was not available, and further review of past experience with thymic cells or factors revealed inconsistent and incomplete responses. Because of the patient's worsening clinical and immunologic status, BMT was performed, with her histocompatible brother as donor. The patient has had a good clinical and immunologic response to BMT, with evidence of T cell engraftment, improved B cell function, and increased levels of serum FTS. This experience indicates that minimal thymic influence is necessary for successful BMT and that patients with DiGeorge syndrome with significant T cell deficiency may benefit from this treatment.

Topics: Adult; Age Factors; B-Lymphocytes; Bone Marrow; Bone Marrow Transplantation; DiGeorge Syndrome; Evaluation Studies as Topic; Female; Humans; Immunoglobulin G; Immunologic Deficiency Syndromes; Infant, Newborn; Leukocyte Count; Male; T-Lymphocytes; Thymalfasin; Thymic Factor, Circulating; Thymosin

Topics: BCG Vaccine; Bone Marrow Transplantation; Female; Humans; Immunologic Deficiency Syndromes; Infant; Sepsis; Staphylococcal Infections; Thymosin; Thymus Gland; Tuberculosis

The restorative effect of thymosin fraction 5 (TF5) on the thymus of gamma-irradiated mice was examined. Four different mouse strains were used in this study since earlier work determined that the degree of response to TF5 is strain dependent. The responsiveness to comitogenic effect of interleukin 1 (IL-1) was used to measure the rate of recovery of immunocompetent cells in the thymus, since only more mature PNA-, Lyt-1+-2- medullary cells respond to this monokine. Contrary to several earlier reports that radioresistant cells repopulating the thymus within the first 10 days after irradiation are mature, corticosteroid resistant, immunocompetent cells, the thymic cells from irradiated mice in all strains used had greatly reduced responses to IL-1. Daily intraperitoneal injections of TF5 increased significantly the responses of thymic cells to IL-1 in 10- to 13-weeks-old C57Bl/KsJ, C57Bl/6, C3H/HeJ, and DBA/1 mice. Older mice, 5 months or more in age, of DBA/1 strain did not respond to treatment with TF5. However, C3H/HeJ mice of the same age were highly responsive. In conclusion, (1) cells repopulating the thymus within 12 days after irradiation contain lower than normal fraction of mature IL-1 responsive cells, (2) thymic hormones increase the rate of recovery of immunocompetent cells in the thymus, and (3) the effect of thymic hormones is strain and age dependent.

Topics: Animals; Female; Gamma Rays; Immunologic Deficiency Syndromes; Interleukin-1; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Radiation Injuries, Experimental; T-Lymphocytes; Thymosin; Thymus Gland

Immunodeficient dwarfism in Weimaraner dogs was characterized by failure to grow, emaciation, growth hormone (GH) deficiency, decreased lymphocyte blastogenic responsiveness to mitogens, lack of thymus cortex, and recurrent infections usually resulting in death. Affected pups did not respond to conventional supportive therapy, but did respond to treatment with thymosin fraction 5. Response to therapy with bovine GH was monitored by clinical observation, histopathologic examination of thymic biopsy material, lymphocyte blastogenic responsiveness to nonspecific mitogens, and radioimmunoassay of thymosin alpha 1 concentration in the serum. Growth hormone therapy (0.1 mg/kg of body weight/dose, 14 doses) during a 1-month period in 2 immunodeficient dwarf pups resulted in clinical improvement and a marked increase in the thickness and cellularity of the cortex of the thymus. Immunodeficient dwarf pups were not deficient in serum thymosin alpha 1 before GH therapy. Growth hormone therapy was not associated with a consistent increase in serum thymosin alpha 1 concentration or lymphocyte blastogenic responsiveness to mitogens.

Topics: Animals; Dog Diseases; Dogs; Dwarfism; Female; Growth Hormone; Immunologic Deficiency Syndromes; Lymphocyte Activation; Thymalfasin; Thymosin; Thymus Gland

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.

Topics: Antibodies, Monoclonal; Antigens, Surface; Cell Differentiation; Child, Preschool; Epithelium; Female; Humans; Immune Sera; Immunity, Cellular; Immunologic Deficiency Syndromes; Infant; Male; T-Lymphocytes; Thymosin; Thymus Gland; Thymus Hormones

Topics: Antibodies, Monoclonal; Child; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Male; T-Lymphocytes; Thymosin

Topics: Adult; Homosexuality; Humans; Immunologic Deficiency Syndromes; Infections; Male; Sarcoma, Kaposi; Thymalfasin; Thymosin; Thymus Hormones

Topics: Culture Media; Humans; Immunologic Deficiency Syndromes; Myasthenia Gravis; Nucleotidases; T-Lymphocytes; Theophylline; Thymosin; Thymus Gland

Topics: B-Lymphocytes; Cells, Cultured; Dysgammaglobulinemia; Humans; Hypoparathyroidism; Immunologic Deficiency Syndromes; Infant, Newborn; Lymphocyte Activation; Male; Rosette Formation; T-Lymphocytes; Thymosin; Thymus Hormones

A child with the cerebro-hepato-renal syndrome of Zellweger, who was originally diagnosed as having the DiGeorge syndrome, was studied and transplanted unsuccessfully with cultured thymus. The pertinent literature is reviewed and the importance of distinguishing the two disorders emphasized. Autopsy studies reveal that transplanted cultured thymic fragments can attract lymphoid aggregates as early as 2 wk after transplantation.

Topics: Abnormalities, Multiple; Brain; Diagnosis, Differential; DiGeorge Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Kidney; Liver; Lymphoid Tissue; Male; Mitochondria; Rosette Formation; Syndrome; Thymosin; Thymus Gland

Thymosin fraction 5 contains a family of polypeptides with varying biological activities. Current efforts in the thymosin research program are involved in further chemical characterization of thymosin peptides and evaluation of clinical immunotherapeutic protocols. Recent clinical studies with thymosin fraction 5 have shown therapeutic potentials for treatment of patients with primary immunodeficiency diseases and cancer.

Topics: Cyclic GMP; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Neoplasms; Thymosin; Thymus Hormones

Reconstruction of the T-cell immune defect in patients with the DiGeorge syndrome has been accomplished in the past by fetal thymus transplantation. Because of the risk of fatal graft-versus-host reaction with fetal thymus transplantation in patients with abnormal T-cell immunity, we have examined the effects of a thymus tissue extract, thymosin fraction 5, on the in vitro and in vivo immune function in children with the DiGeorge syndrome. T-cell numbers were increased with thymosin F5 in vitro in three of five patients. T-cell number and function was improved in three of four patients treated with thymosin F5 in vivo. Spontaneous improvement in the immune function of these patients cannot be excluded. These results suggest, however, that further trials with thymosin F5 therapy may be indicated in patients with the DiGeorge syndrome.

Topics: DiGeorge Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Thymosin; Thymus Hormones

Topics: alpha 1-Antitrypsin Deficiency; Humans; Immunologic Deficiency Syndromes; Thymosin

Topics: DiGeorge Syndrome; Drug Hypersensitivity; Histamine Release; Humans; Immunoglobulin E; Immunologic Deficiency Syndromes; Infant, Newborn; Leukocytes; Male; Streptolysins; T-Lymphocytes; Thymidine; Thymosin; Thymus Hormones

Topics: Adult; Ataxia Telangiectasia; Candidiasis; Chronic Disease; DiGeorge Syndrome; Eczema; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Lymphocyte Culture Test, Mixed; Male; Thymosin; Thymus Gland; Thymus Hormones; Wiskott-Aldrich Syndrome

Topics: Bacterial Infections; Down Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Male; Mycoses; Thymosin; Thymus Hormones

Two siblings with adenosine deaminase deficiency were studied before and during "enzyme replacement" therapy (partial exchange transfusions with normal red cells containing the missing enzyme). The younger sib showed improvement of immunologic function during red-cell therapy alone, whereas in the older sib this improvement occurred only when the transfusions were supplemented by thymosin injections. Their clinical courses correlated with in vitro findings: lymphocytes from the younger sib differentiated to T-cell-rosette-forming cells upon addition of adenosine deaminase alone; lymphocytes from the older sibling required supplemental thymosin to form these cells. Thymic factors appear to influence the response to transfusion therapy in some patients deficient in adenosine deaminase, and supplementation of red-cell transfusion with thymic factors may be required.

Topics: Adenosine Deaminase; Erythrocytes; Exchange Transfusion, Whole Blood; Humans; Immunologic Deficiency Syndromes; Infant; Lymphocytes; Male; Nucleoside Deaminases; Rosette Formation; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Blood Cell Count; Humans; Hypersensitivity, Delayed; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Infant; Lymphocyte Activation; Lymphocytes; Male; Rosette Formation; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Animals; Candidiasis, Chronic Mucocutaneous; Cattle; Cell Differentiation; DiGeorge Syndrome; Epithelium; Humans; Immunologic Deficiency Syndromes; Mice; T-Lymphocytes; Thymic Factor, Circulating; Thymopoietins; Thymosin; Thymus Gland; Thymus Hormones; Wiskott-Aldrich Syndrome; Zinc

The therapy of inborn or acquired defects of the cellular immune function is still in an experimental stage. Basicly, it is possible to replace the non-functioning T-cells by immunocompetent lymphocytes. Bone marrow, fetal liver and/or thymus, or cultivated thymus can serve as the source of such cells. Under certain conditions humoral factors derived from immunocompetent lymphocytes can induce a lacking immune response. Possibilities as well as limitations of these two therapeutic concepts are discussed.

Topics: Bone Marrow Cells; Child; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Liver; Lymphocytes; Thymosin; Thymus Gland; Transfer Factor

Topics: Adenosine Deaminase; Blood Transfusion; Erythrocyte Transfusion; Humans; Immunologic Deficiency Syndromes; Infant; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Nucleoside Deaminases; Plasma; Rosette Formation; Thymosin

Topics: Chickenpox; Female; Humans; Immunologic Deficiency Syndromes; Lymphoid Tissue; Pentosyltransferases; Purine-Nucleoside Phosphorylase; T-Lymphocytes; Thymosin; Uridine

Topics: Cell Differentiation; Child; Cyclic AMP; Hematopoietic Stem Cells; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; Rosette Formation; Thymosin; Thymus Hormones

Our current research program centers around the biologic and chemical characterization of the family of polypeptides present in thymosin fraction 5. A system of nomenclature has been developed and the peptides are being systematically isolated and chemically characterized. Thymosin fraction 5 and its component parts influence a variety of lymphocyte properties including cyclic nucleotide levels, migration inhibitory factor production, T-dependent antibody production, and expression of certain surface markers. Thymosin is being used in clinical trials to investigate its effects on immunodeficiency diseases, malignant diseases, and autoimmune diseases.

Topics: Animals; Autoimmune Diseases; Chemical Phenomena; Chemistry; Cyclic AMP; Cyclic GMP; Drug Evaluation; Guinea Pigs; Humans; Immunologic Deficiency Syndromes; In Vitro Techniques; Lymphocytes; Neoplasms; T-Lymphocytes; Thymosin; Thymus Hormones

Thymosin has no effect in vitro on cyclic AMP levels in thymocytes. However, when thymosin was injected into patients lacking "serum factor" (SF) activity, it induced the appearance of SF or SF-like activity and the disappearance of target cells for SF among the peripheral blood lymphocytes of the treated patients. On the other hand, when thymosin was injected into one patient with normal SF activity, it induced a marked decrease of SF activity and the appearance of target cells for SF among the peripheral blood lymphocytes of this particular patient.

Topics: Animals; Child; Child, Preschool; Cyclic AMP; Female; Humans; Immunologic Deficiency Syndromes; In Vitro Techniques; Infant; Infant, Newborn; Male; Mice; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Adolescent; Agammaglobulinemia; Ataxia Telangiectasia; Burkitt Lymphoma; Candidiasis, Cutaneous; Child; Child, Preschool; Chronic Disease; Female; Humans; Immunologic Deficiency Syndromes; Lymphatic Diseases; Male; Middle Aged; Syndrome; T-Lymphocytes; Thymosin; Thymus Gland; Thymus Hormones

Topics: Chemical Phenomena; Chemistry; Humans; Immunologic Deficiency Syndromes; Neoplasms; Thymosin; Thymus Hormones

We report on the in vitro effect of a thymic factor (TF) extracted from pig thymuses, on human lymphoid cells from umbilical cord blood and from peripheral blood of 8 T cell-deficient patients. E rosette formation was not affected by TF when tested on cells from peripheral blood of normal adults. With cells from umbilical cord blood of 13 healthy, full-therm newborn babies, the difference between the percent (mean) of ERFCs before (16.31 +/- 11.13) and after (28.85 +/- 17.10) incubation with TF was statistically significant (p less than 0.05). In most samples, TF transformed about 10-20% of the cells. In the T cell-deficient group the increase in ERFCs of the peripheral blood lymphocytes, though consistent, was variable in degree from case to case. Our data indicate that precursor cells in some individuals with T cell deficiency are very sensitive to TF. Patients with highly responsive precursors appear to be the best candidates for a therapeutic approach with TF when thymus transplant is not possible.

Topics: Child; Child, Preschool; Fetal Blood; Humans; Immunologic Deficiency Syndromes; Immunologic Techniques; Infant; Infant, Newborn; Lymphocyte Activation; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Humans; Immunologic Deficiency Syndromes; Immunologic Techniques; Neoplasms; Thymosin; Thymus Hormones

Topics: Animals; Cattle; Europe; History, 19th Century; History, 20th Century; History, Ancient; Humans; Immunologic Deficiency Syndromes; Mice; Neoplasms; T-Lymphocytes; Thymectomy; Thymosin; Thymus Gland; Thymus Hormones; United States

Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct immunofluorescence. A receptor for the activated C3 complement component was detected on 27-47 percent of his lymphocytes. Only 4-12 percent of the peripheral blood lymphocytes formed spontaneous rosettes with sheep erythrocytes (E-R). In general, no blastogenesis was detected in lymphocyte cultures stimulated with pokeweed mitogen or phytohemagglutinin although transient slightly positive responses to both mitogens were occasionally observed. Incubation of lymphocytes with bovine thymosin Fraction V did not increase the percentage of E-R nor induce lymphocyte blastogenesis in the presence of phytohemagglutinin.

Topics: B-Lymphocytes; Cell Membrane; Child, Preschool; Epitopes; Germ-Free Life; Humans; Immune Adherence Reaction; Immunoglobulin M; Immunologic Deficiency Syndromes; Lectins; Lymphocyte Activation; Male; Sex Chromosomes; T-Lymphocytes; Thymosin

Topics: Animals; Child; Child, Preschool; Female; Humans; Hypersensitivity, Delayed; Immune Adherence Reaction; Immunity, Cellular; Immunologic Deficiency Syndromes; Infant; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Mice; Mice, Inbred Strains; Mitogens; Neoplasms; Thymosin; Thymus Extracts

The present report describes an infant with severe combined immunodeficiency and cartilage-hair hypoplasia whose lymphocytes responded to thymosin in vitro. Immunologic evaluation was undertaken at 4 1/2 months of age following a history of recurrent severe infection. Family history included three cousins who died in early infancy, one from streptococcal meningitis and pneumonia, one from generalized varicella, and another from reticuloendotheliosis. Quantitative immunoglobulins were markedly depressed: IgG 141, IgA 0, and IgM 24 mg/100 ml. There was an absolute lymphopenia, multiple skin tests were negative, and in vitro lymphocyte responses to mitogens and antigens were depressed. Spontaneous E rosette determinations were 21% compared with control values of 65.7%. Erythrocyte adenosine deaminase (ADA) activity was normal. The patient's E rosette formation increased in the presence of thymosin, fraction 5, reaching a maximum of 56% with a concentration of 500 mug thymosin. Blastogenic responses to phytohemagglutinin also increased in the presence of thymosin. Transplantation of 24-week fetal thymus in Millipore diffusion chambers and subsequently transplantation of 18-week fetal thymus by intraperitoneal injection was accomplished. E rosettes increased to 35-40% and blastogenic responses to mitogens increased. Eight days after the second transplant the patient underwent a mild graft vs. host reaction which subsided after 1 week and mitogen blastogenic responses again increased to 5-8 times previous values, but still well below control ranges. Repeated episodes of pulmonary infection ensued, cor pulmonale resulted, and the clinical course was relentlessly downhill with the patient expiring from respiratory failure 5 months after transplantation.

Topics: Cartilage; Hair; Humans; Immunologic Deficiency Syndromes; Infant; Lymphocytes; Male; Mitogens; Thymosin; Thymus Gland; Thymus Hormones; Transfer Factor; Transplantation, Homologous

Topics: B-Lymphocytes; Child; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Immunotherapy; T-Lymphocytes; Thymosin; Thymus Gland; Transplantation, Homologous

In preparation for the use of bovine thymosin, a thymic hormone, as a specific T cell stimulator in immunodepressed patients, we studied its effect on E rosette formation of peripheral lymphocytes from patients with (1) advanced malignancies, (2) extensive burns, and (3) septicemia. E rosette formation in vitro with and without thymosin was evaluated in 52 patients with carcinoma of the breast (25) or lung (27) in relation to adjuvant therapy and/or surgery. The depression of E rosettes in cancer patients was most striking when adjuvant therapy, irradiation, and/or chemotherapy were used; in 20 patients this was elevated by incubation with thymosin. There was a delay in recovery of depressed E rosette levels after radical mastectomies in four patients, recovery being accelerated by thymosin. In ten burn patients (40 to 80 percent of body surface area, second and third degree burns), the depression in E rosette levels occurred in the first week and was most marked in 3 to 4 weeks. In eight patients this was elevated by thymosin in vitro. In four septic patients, all undergoing operation, serial studies suggested that recovery from sepsis was accompanied by spontaneous rise in E rosette levels. This process was accelerated by thymosin in vitro. This study as well as previous experiments with animals suggest that thymosin may influence depressed host resistance favorably by increasing T-cell-mediated immunity.

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Burns; Child; Child, Preschool; Female; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; In Vitro Techniques; Lung Neoplasms; Male; Middle Aged; Sepsis; T-Lymphocytes; Thymosin; Thymus Extracts

A 6 1/2-month-old male with severe combined immunodeficiency (SCID) had a low percentage and number of T cells (11%; 241/mm3) and a high percentage and number of B cells (52%; 1187/mm3) and null cells (37%; 868/mm3). In vitro studies were performed to determine if this child's primary defect involved differentiation of both T and B lymphocytes or if failure of B lymphocytes to differentiate into immunoglobulin producing cells was secondary to T lymphocyte abnormalities. Immunoglobulin production by lymphocytes in response to polyclonal mitogens (pokeweed mitogen and foetal calf serum) was measured by pulse-labelling cells with 3H-leucine and then precipitating cytoplasmic and secreted immunoglobulins with polyvalent anti-human immunoglobulin and S. aureus (Cowan strain I) protein A. The patient's lymphocytes did not synthesize immunoglobulins in vitro in response to mitogens. They did not suppress synthesis of immunoglobulins by normal lymphocytes. However, addition of normal purified T cells, which themselves did not synthesize immunoglobulins, enabled the patient's B lymphocytes to become immunoglobulin synthesizing and secreting cells. Gamma, mu, and light chains were secreted. This suggests that the primary abnormality was in the T-cell axis at the level of lymphoid stem cells or prothymocytes and that failure of B lymphocytes to become immunoglobulin-producing cells was secondary to this defect.

Topics: Antibody-Producing Cells; B-Lymphocytes; Cell Differentiation; Cell Division; Dysgammaglobulinemia; Humans; Immunization, Passive; Immunoglobulin G; Immunoglobulins; Immunologic Deficiency Syndromes; In Vitro Techniques; Infant; Leukocyte Count; Male; Mitogens; Monocytes; Receptors, Antigen, B-Cell; T-Lymphocytes; Thymosin

A male infant with bilateral iris coloboma who had had repeated infections and malabsorption was studied. The levels of total lymphocytes and of T and B cells were normal or high, but IgA became undectable and IgG low, whereas IgM was normal. His lymphocytes did not respond to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen (PWM) or in mixed lymphocyte reactions (MLR), nor did they respond in vitro when thymosin was included in the test systems. He was skin-test-negative, even to dinitrochlorobenzene. His crudely isolated T lymphocytes and the supernatant of his PHA-stimulated lymphocytes inhibit the response of normal lymphocytes to PHA, PWM, and in MLR. During thymosin treatment skin test and lymphocyte reactivity to mitogen remained negative. He became faintly positive in MLR, and the suppressor activity in the supernatant of his PHA-stimulated lymphocytes no longer inhibited the response of normal lymphocytes to PHA, PWM, or in MLR. In parallel with thymosin treatment he showed quite marked clinical improvement.

Topics: B-Lymphocytes; Coloboma; Concanavalin A; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Infant; Iris; Lectins; Leukocyte Count; Lymphocyte Activation; Male; Mitogens; Skin Tests; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Adult; Animals; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Cattle; Cell Differentiation; Cell Separation; Cells, Cultured; Concanavalin A; Epitopes; Erythrocytes; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Infant; Lectins; Male; Mitomycins; Parathyroid Glands; Sheep; Spleen; Syndrome; T-Lymphocytes; Thymidine; Thymosin; Thymus Extracts; Thymus Gland; Tissue Extracts; Transfer Factor; Tritium

Topics: Amino Acids; Animals; Cattle; Chromatography, Gel; Cytotoxicity Tests, Immunologic; Electrophoresis, Polyacrylamide Gel; Graft vs Host Reaction; Humans; Immune Adherence Reaction; Immune Sera; Immunodiffusion; Immunologic Deficiency Syndromes; Iodine Radioisotopes; Lymphocyte Culture Test, Mixed; Mice; Molecular Weight; Rabbits; Radioimmunoassay; Sodium Dodecyl Sulfate; T-Lymphocytes; Thymosin; Thymus Extracts

Topics: Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Cell Separation; Histocompatibility; Humans; Immunologic Deficiency Syndromes; Infant; Lymphocyte Activation; Mitogens; Peptides; Protein Biosynthesis; RNA; T-Lymphocytes; Thymosin; Thymus Extracts; Transplantation, Homologous

Topics: Adult; Agammaglobulinemia; Ataxia Telangiectasia; Child; Dose-Response Relationship, Drug; Female; Histocompatibility Antigens; Humans; Immune Adherence Reaction; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Infant; Liver; Mosaicism; Nasopharyngeal Neoplasms; Parathyroid Glands; Respiratory Tract Infections; Spleen; Syndrome; T-Lymphocytes; Thymosin; Thymus Extracts; Thymus Gland; Tissue Extracts; Transplantation, Homologous; Wiskott-Aldrich Syndrome

Topics: B-Lymphocytes; Female; Humans; Hypersensitivity, Delayed; Immune Adherence Reaction; Immunoglobulins; Immunologic Deficiency Syndromes; Thymosin; Thymus Extracts

Topics: Age Factors; Animals; Cell Differentiation; Dogs; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Lupus Erythematosus, Systemic; Mice; Molecular Weight; Neoplasms; T-Lymphocytes; Thymosin; Thymus Extracts