Analysis of site of action of a choriocarcinoma-derived immunoregulatory factor on IL-2-mediated T cell responses.
We have investigated the functional ability of a choriocarcinoma-cell-derived factor to block human T cell responses and the factor's immunoregulatory site of action on the T cell signal transduction pathway. The factor completely suppressed human T cell responses activated by phorbol ester and calcium ionophore, reagents which strongly stimulate IL-2-mediated T cell responses. It failed to inhibit CD 25 expression and IL-2 production by T cell blasts in the T cell activation phase, but completely blocked recombinant IL-2-induced proliferation of T cell blasts in the T cell proliferation phase. Absorption experiments with the factor and Con A-induced T cell blasts as well as [125I]IL-2 binding experiments with T cell blasts revealed that the factor acted on the physiological events occurring after IL-2-mediated stimulation of IL-2 receptor complexes, demonstrating no interaction of the factor with either IL-2 molecules or IL-2 receptor complexes. Moreover, it suppressed murine IL-2 dependent T cell line proliferation, suggesting the presence of common pathways in human and murine T cell proliferation. The biological and immunological significance of the factor during pregnancy and in the immunosuppressed tumor-bearing hosts are discussed.
Matsuzaki
N
N
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Okada
T
T
Kameda
T
T
Negoro
T
T
Saji
F
F
Tanizawa
O
O
D000001:Calcimycin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; D003208:Concanavalin A; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate