Nakahara memorial lecture. Regulation of T lymphocyte responses: interactions among receptors.
Murine helper T lymphocytes (HTL) have been categorized on the basis of the lymphokines they secrete. TH1 cells produce interleukin 2 (IL-2), interferon-gamma (IFN-gamma), and lymphotoxin, whereas TH2 cells produce IL-4 and IL-5 but not IL-2 or IFN-gamma. Both cell types apparently can produce IL-3, granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor. We have found that there is at least one additional subset which secretes IL-4 and IFN-gamma. These helper T lymphocyte subsets also respond differently to immunoregulatory processes. T cell clones of all subtypes can proliferate in response to exogenous IL-2, but IL-4 apparently induces a proliferative response only in those subsets that produce IL-4. IFN-gamma inhibits the proliferation of TH2 clones, but does not affect the proliferation of TH1 clones, cytolytic T lymphocyte (CTL) clones, or cells that produce both IL-4 and IFN-gamma. TH1 cells pretreated with a saturating concentration of IL-2 do not proliferate when stimulated with anti-CD3 monoclonal antibody (mAb). However, proliferation of TH2 cells is enhanced by IL-2 pretreatment, while the TH1 clones or CTL clones through the T cell receptor (TCR) profoundly inhibits IL-2-induced proliferation of those cells, whereas such stimulation either has very little effect or augments the proliferation of IL-4-producing clones. Collectively, these data suggest that the combined influence of these cytokines and intensity of TCR stimulation may determine which cell types expand in number during a particular immunological situation.
Fitch
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Ben May Institute, Committee on Immunology, Chicago, Illinois.
Gajewski
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Nau
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Schell
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Otten
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma