INTERLEUKIN-10, INTERLEUKIN-12, AND TUMOR-NECROSIS-FACTOR-ALPHA DIFFERENTIALLY INFLUENCE THE PROLIFERATION OF HUMAN CD8(-CELL CLONES() AND CD4(+) T)

Activation and proliferation of human T lymphocytes in vitro can be ob tained by various stimuli including specific antigens, mitogens, and c ytokines. Here we describe the effect of interleukin-10, interleukin-1 2 and tumor necrosis factor-alpha on the interleukin-2 dependent proli feration and function of established human CD4(+) and CD8(+) alloreact ive T-cell clones in the absence of antigen presenting cells. IL-12 an d TNF-alpha both demonstrated an inhibitory effect on the proliferatio n of CD8(+) cytotoxic T lymphocyte clones, whereas IL-10 enhanced the proliferation. IL-12-induced inhibition of CD8(+) CTL clones was not m ediated by the endogenous production of TNF-alpha by these clones. The strong inhibitory effect of IL-12 and TNF-alpha did not result in apo ptosis. These cytokines did not alter the cytotoxicity of CD8(+) CTL c lones. When CD4(+) T-cell clones were tested in the absence of APC, no significant change in IL-2-dependent proliferation due to IL-10, IL-1 2, and TNF-alpha could be measured. Since these effects on established CTL clones are in contrast to the effects of IL-10, IL-12, and TNF-al pha during the induction phase of immune responses, a dichotomy of imm unomodulatory cytokines such as IL-10, IL-12, and TNF-alpha early and late in the immune response is suggested.