Interleukin-10, interleukin-12, and tumor necrosis factor-α differentially influence the proliferation of human CD8⁺ and CD4⁺ T-cell clones

Abstract

 Activation and proliferation of human T lymphocytes in vitro can be obtained by various stimuli including specific antigens, mitogens, and cytokines. Here we describe the effect of interleukin-10, interleukin-12 and tumor necrosis factor-α on the interleukin-2 dependent proliferation and function of established human CD4⁺ and CD8⁺ alloreactive T-cell clones in the absence of antigen presenting cells. IL-12 and TNF-α both demonstrated an inhibitory effect on the proliferation of CD8⁺ cytotoxic T lymphocyte clones, whereas IL-10 enhanced the proliferation. IL-12-induced inhibition of CD8⁺ CTL clones was not mediated by the endogenous production of TNF-α by these clones. The strong inhibitory effect of IL-12 and TNF-α did not result in apoptosis. These cytokines did not alter the cytotoxicity of CD8⁺ CTL clones. 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-12, and TNF-α could be measured. Since these effects on established CTL clones are in contrast to the effects of IL-10, IL-12, and TNF-α during the induction phase of immune responses, a dichotomy of immunomodulatory cytokines such as IL-10, IL-12, and TNF-α early and late in the immune response is suggested.