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.