thymic-factor--circulating and Acquired-Immunodeficiency-Syndrome

Recent immunological research has concentrated on the complex and subtle interactions between T cells, B cells and accessory cells. In these studies, little attention has been given to the adult thymus gland. Modern textbooks of disease and anatomy all stress that the gland undergoes fatty involution with age in man but omit reference to the statements here and there in the literature that the gland is active and produces lymphocytes throughout life. To suggest that the bone marrow, which also builds up fat throughout life, is atrophic and not important to adult man would deny all modern hematological concepts. Yet few people today take a parallel view of the thymus except perhaps those investigating aging and thymic hormones. In both of these areas of research it is obvious that the thymus must be active throughout life for continued good health. This brief review urges that a thorough understanding of the vital importance of the thymus in adult life is now needed. From it could emerge a new philosophy on the treatment of immune diseases in both the young (SCID and AIDS patients) and in the aged (autoimmune conditions and cancers) and it would aid our treatment of patients recovering from illness and from many drug treatments.

Topics: Acquired Immunodeficiency Syndrome; Aging; Animals; Cell Cycle; Cell Movement; DiGeorge Syndrome; Hematopoiesis; Humans; Immunologic Deficiency Syndromes; Organ Size; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones; Time Factors

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

Functional, excessive-possibly temporary-deficiencies of the trace element zinc can change immune functions prematurely from predominantly cellular Th1 responses to humoral Th2 responses. T helper (Th1) cells produce cytokines such as interleukin-2 (IL-2) and interferon gamma, thereby controlling viral infections and other intracellular pathogens more effectively than Th2 responses through cytokines such as IL-4, IL-5, IL-6 and IL-10. The accelerated shift from the production of extra Th1 cells during these cellular immune activities to more Th2 cells with their predominantly humoral immune functions, caused by such a zinc deficiency, adversely influences the course of diseases such as leprosy, schistosomiasis, leishmaniasis and AIDS, and can result in allergies. It is noteworthy that AIDS viruses (HIVs) do not replicate in Th1 cells, which probably contain more zinc, but preferentially in the Th0 and Th2 cells; all the more so, because zinc and copper ions are known to inhibit intracellular HIV replication. Considering the above Th1/Th2 switch, real prospects seem to be offered of vaccination against such parasites as Leishmania and against HIVs.

Topics: Acquired Immunodeficiency Syndrome; Animals; Apoptosis; Cytokines; HIV; Humans; Hypersensitivity, Immediate; Leishmania; Liver; Mast Cells; Mice; Models, Biological; Murine Acquired Immunodeficiency Syndrome; Th1 Cells; Th2 Cells; Thymic Factor, Circulating; Vaccination; Virus Replication; Zinc

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Biological Availability; Humans; Thymic Factor, Circulating; Zinc

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Humans; Thymic Factor, Circulating; Thymus Hormones; Zinc

Twenty-five children with acquired immune deficiency syndrome (AIDS) or AIDS-related complex had a characteristic pattern of T cell deficiency. Abnormally low plasma thymulin levels preceded the development of peripheral blood T cell abnormalities. In contrast to patients with congenital T cell deficiencies, our patients had elevated serum levels of thymosin-alpha 1. Treatment with thymosin fraction 5 in three children with AIDS resulted in only transient clinical and immunologic improvement.

Topics: Acquired Immunodeficiency Syndrome; Child; Child, Preschool; Deltaretrovirus; Humans; In Vitro Techniques; Infant; T-Lymphocytes; Thymalfasin; Thymic Factor, Circulating; Thymosin; Thymus Hormones

Thymic secretory function was assessed by determining levels of circulating thymulin-like activity in plasma of 21 pediatric patients infected with the HTLV-III/LAV retrovirus. All the patients had serum antibodies against p41 antigens of HTLV-III on Western blot analyses. In accordance with the latest definition established by the Centers for Disease Control, 14 patients had the acquired immunodeficiency syndrome (AIDS) and the remaining 7 were classified as having AIDS-related complex. Their ages ranged from 1 to 7 years, with 10 being less than 1 year of age. Circulating thymulin activity, normally highest in healthy children under 15 years of age, was undetectable in 11 patients and below normal range for age in the remaining. OKT4/OKT8 ratios of T-cell subsets in peripheral blood were below normal in the majority of patients. Our findings suggest that thymic epithelial injury may be an early event in HTLV-III/LAV-related disease and may precede the development of clinical and/or immunologic aberrations.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Age Factors; Child; Child, Preschool; Humans; Infant; Infant, Newborn; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones

The authors investigated by immunofluorescence the thymic epithelium from AIDS patients, using several structural and functional markers of this tissue. In AIDS thymus, the epithelial reticular pattern was lost; and instead, clusters of round or spindle-shaped cells (assessed by their keratin content) were found. In addition, regions of epithelial necrosis, with loss of cell limits, were frequently observed. Thymulin content was decreased, and a partial loss of differentiation antigens of the thymic epithelium was also detected. The authors showed the presence of immunoglobulins and elements of the complement system directly bound to AIDS thymic epithelium, but not in any of the controls studied, including thymuses from patients who died after a long period of agony. These data suggest that the thymic epithelium can be included among the target tissues in AIDS, possibly by an indirect mechanism of autoimmune destruction.

Topics: Acquired Immunodeficiency Syndrome; Adult; Child, Preschool; Epithelium; Female; Fluorescent Antibody Technique; Histocompatibility Antigens Class II; Histocytochemistry; HLA Antigens; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Infant; Male; Thymic Factor, Circulating; Thymus Gland

This paper presents a case in which treatment of acquired immunodeficiency syndrome (AIDS) was attempted with thymic humoral factor (THF). The capacity of THF for immunoenhancement and modulation of the immune response has been demonstrated in other conditions. The patient, a 24-year old black male homosexual from San Francisco, had experienced fever spikes, malaise, fatigue, anorexia, gradual vision loss, and weight loss over an 8-month period. Lymphopenia, T cell deficiencies, and imbalances in T cell subpopulations established the diagnosis of AIDS. Treatment with arabinoside A and fibroblast interferon was not effective. THF was then administered by daily injections for 3 weeks. At the end of the 2nd week of treatment, increased alertness and appetite were noted. Also documented was a transient increase in circulating lymphocytes, T cells, and helper cells. However, at the end of the 3rd week, the patient developed bronchopneumonia followed by renal failure and died in an acute encephalopathic state. Only 1 other (unsuccessful) attempt to treat an advanced case of AIDS with a thymic hormone has been reported. It is suggested that THF treatment might be more effective if offered at a very early stage of AIDS. It is hypothesized that a sufficient pool of precursor T cells is required to serve as target cells for immune modifiers such as THF. This precursor pool probably shrinks beyond rescue in the advanced stages of AIDS. The authors are currently involved in trials of immunomodulation with THF at early stages of immune impairment in pre-AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Immunotherapy; Leukocyte Count; Lymphocytes; Male; Thymic Factor, Circulating; Thymus Hormones

Topics: Acquired Immunodeficiency Syndrome; Adult; Homosexuality; Humans; Infections; Male; Middle Aged; Sarcoma, Kaposi; Thymic Factor, Circulating; Thymus Hormones