Most T lymphocytes can be divided into two subsets, one consisting of cells expressing the CD4 cell surface structure and the other consisting of cells expressing CD8; this distinction generally correlates with function. CD4+ cells are helper T lymphocytes (HTL) which exert (or carry out) their "helper" functions through secreted lymphokines which affect the activity of the T cells that produce them in an autocrine fashion, as well as modulate responses of other cells in a paracrine fashion; their Responses are restricted by class II MHC molecules. CD8+ cells are cytolytic T lymphocytes (CTL) which also secrete some lymphokines in responses to antigenic stimulation, although the array of lymphokines produced generally is more restricted compared to HTL; their responses usually are class I MHC-restricted. Cloned populations of normal T cells have greatly facilitated the study of activation requirements are functional characteristics of these T cell subsets. Although the specificity of T cell responses is conferred by the T cell receptor for antigen (TCR), effector functions are influenced by additional factors.

Murine CD4+ HTL clones can be further categorized into at least two distinct subsets, designed TH1 and TH2, on the basis of the particular array of lymphokines they secrete; this distinction correlates with what has traditionally been described as cellular and humoral immunity. TH1 but not TH2 cells appear to mediate delayed-typed hypersensitivity while TH2 cells provide efficient help for B cell responses.

Effects of lymphokines on lymphocyte functions: IFN-gamma inhibits the proliferation of TH2 clones but not TH1 or CTL clones; lymphokine production by TH2 cells apparently is unaffected by IFN-gamma. When fresh antigen-specific HTL clones are derived using only rIL-2 as a source of growth factors, TH2 cells are preferentially obtained. In contrast, TH1 cells are preferentially derived in the presence if rIL-1 and rIFN-gamma. Thus, the presence of IFN-gamma during the course of an immune response can result in the selective expansion of cells of the TH1 phenotype. Also, pretreatment of TH1, but not TH2 or CTL cells with IL-2 results is decreased lymphokine production and proliferation in response to subsequent stimulation via the TCR. This antigen-unresponsive state appears to involve a down-regulation of calcium-dependent signaling.

Signalling mechanisms in T cell subsets: IL-2-dependent proliferation of TH1 and CTL cells is dramatically inhibited by high concentrations of immobilized anti-TCR monoclonal antibody (mAb). This inhibitory effect appears to be mediated, in apart, by elevated intracellular free calcium. In contrast, TH2 cells proliferation in response to IL-2 either is unaffected or if augmented by immobilized anti-TCR. This and other evidence suggesting that at least some of the TCR-associated signal transduction mechanisms differ in TH1 CTL, and TH2 clones.