Growth factor production and requirements during the proliferative response of human T lymphocytes to anti-CD3 monoclonal antibody.
Anti-CD3 was administered with three different accessory stimuli to purified populations of human T cells. Sepharose conjugated anti-CD3, monocytes, and PMA each could induce the p55 component of the IL-2R as well as responsiveness to exogenous IL-2. Sepharose anti-CD3 did not induce IL-2, although the levels of IL-2 protein and mRNA were 10 to 30 times higher with PMA than with monocytes. Despite these differences in IL-2 production, the amount of DNA synthesis and the number of lymphoblasts were comparable when monocytes or PMA were used as the accessory stimulus, and the responses were equally sensitive to inhibition by an anti-IL-2R antibody. To pursue the functional relevance of the "supraoptimal" levels of IL-2 that are induced by PMA, anti-CD3-induced lymphoblasts were isolated free of monocytes and challenged with lymphokines. It could be shown that 1) the small amounts of IL-2 in the monocyte-T cell conditioned medium would drive DNA synthesis, but that 2) higher levels of IL-2 (20 to 100 U/ml) were needed to induce IFN-gamma, as well as the mRNA for IL-4 and the p55 IL-2R. We suggest that the capacity to produce high levels of IL-2, as seen with PMA, is required under physiologic conditions for two reasons: to up-regulate the IL-2R when small amounts of Ag rather than large amounts of anti-CD3 are ligands for the T cell, or to induce the release of lymphokines like IL-4 and IFN-gamma from sensitized lymphoblasts.
Granelli-Piperno
A
A
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York.
Keane
M
M
Steinman
R M
RM
D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002469:Cell Separation; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000502:physiology; D015847:Interleukin-4; D007378:Interleukins / Q000302:isolation & purification; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000302:isolation & purification; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012685:Sepharose; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D007378:Interleukins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D012685:Sepharose; D013755:Tetradecanoylphorbol Acetate