thymic-factor--circulating and Leukemia--Lymphoid

Topics: Animals; Cricetinae; Guinea Pigs; Interleukin-2; Lethal Dose 50; Leukemia, Lymphoid; Mice; Thymic Factor, Circulating; Thymopoietins; Thymus Extracts; Thymus Hormones

Topics: Adjuvants, Immunologic; Adolescent; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Leukocyte Count; T-Lymphocytes; Thymus Hormones

Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.

Topics: Aged; Animals; B-Lymphocytes; Cattle; Female; Humans; In Vitro Techniques; Leukemia, Lymphoid; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Thymic Factor, Circulating; Thymus Hormones

The interaction of the synthetic serum thymic factor (FTS, facteur thymique sérique) with a plasma membrane preparation of human T lymphocytes from the lymphoblastoid T cell line 1301 was studied using 3H-labelled FTS (specific activity 120 Ci/mmol). The binding is temperature dependent and function of the concentration of both 3H-labelled FTS and membrane proteins. At 37 degrees C, using 1 nM of 3H-labelled FTS as steady state is observed within 80 min. The binding is reversible, specific and saturable. Scatchard analysis reveals the existence of at least two binding sites with respective Kd of the order of 0.516 +/- 0.2 nM and 110 +/- 27.8 nM with concentration of 0.186 +/- 0.045 pmol and 2.026 +/- 0.367 pmol per mg of membrane protein.

Topics: Binding Sites; Cell Line; Cell Membrane; Humans; Kinetics; Leukemia, Lymphoid; T-Lymphocytes; Temperature; Thymic Factor, Circulating; Thymus Hormones; Tritium

We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis. We further postulated that chronic GVHD, whatever its cause, involves thymic epithelium as a target organ. When tested 11 mo or more posttransplant, patients with chronic GVHD had lower absolute FTS levels (p less than 0.02) and lower age-corrected levels (p = 0.05) than patients without chronic GHVD. Low values in chronic GVHD were associated with the disease itself and not its therapy. These findings show that thymic epithelial secretory function is impaired in chronic GVHD, and this may in part be responsible for the immunodeficiency characteristic of these patients.

Topics: Adolescent; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Child; Child, Preschool; Female; Graft vs Host Reaction; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Thymic Factor, Circulating; Thymus Hormones

Studies carried out in our laboratory during the years indicated that the local xenogeneic graft-versus-host reaction (GVHR) might serve as a useful clinical assay of the immunocompetence of human T lymphocytes. Additional studies were therefore carried out using purified populations of B, T and null cells as well as normal mononuclear cell populations, so as to determine the nature of the cells responsible for induction of the reaction and further delineate the factors capable of modifying this pattern of reactivity. Populations of T cells alone gave the largest reaction whereas both B cells from patients with chronic lymphatic leukemia and null cells from patients with acute lymphatic leukemia failed completely to induce a GVHR. The addition of anti-T-lymphocytic serum abolished the reaction, providing further proof of the role played by T lymphocytes. Thymic hormone (THF) was found to enhance the reaction when applied both in vivo and in vitro. The immunostimulatory agents transfer factor and levamisole also enhanced the GVHR obtained with normal mononuclear cells. Cytoxan was found to have an enhancing effect at low doses and an inhibiting effect at high doses. Trypsin also acted to abolish the GVHR. The combination of two populations of normal mononuclears always gave a larger GVHR, indicating allogeneic antigen stimulation. Depletion of the monocytes from the population of normal mononuclears resulted in a smaller reaction, providing further evidence that monocytes are required for T-lymphocyte antigen-induced reactivity. On the basis of these findings it is proposed that the local xenogeneic GVHR is a useful clinical test for the measurement of immunocompetence of T lymphocytes, for the differential diagnosis of leukemias and for the determination of the effectiveness of THF.

Topics: Animals; Female; Graft vs Host Reaction; Horses; Humans; Leukemia, Lymphoid; Levamisole; Lymphocyte Transfusion; Male; Mice; Monocytes; Phagocytes; Rats; Rats, Inbred Lew; T-Lymphocytes; Thymic Factor, Circulating; Transfer Factor; Transplantation, Heterologous; Trichophytin