INTERLEUKIN 10 PROTECTS ACTIVATED HUMAN T LYMPHOCYTES AGAINST GROWTH FACTOR WITHDRAWAL-INDUCED CELL DEATH BUT ONLY ANTI-FAS ANTIBODY CAN PREVENT ACTIVATION-INDUCED CELL DEATH

Interleukin 10 (IL-10) is a pleiotropic T cell-derived cytokine best known for its negative regulatory effects on T cell immunity. It inhibits responses indirectly by downregulating expression of major histocompatibility complex (MHC) molecules and co-stimulatory molecules such as CD80 on antigen presenting cells as well as directly via its effects on responding cells. On the other hand, IL-10 has been shown to protect activated T cells against apoptosis caused by withdrawal of the major growth factor, IL-2, and allow proliferation of T cells in the absence of IL-2. However, we show here that this IL-10-dependent, IL-2 independent proliferative response is short-lived, and that IL-10-responsive T cells cannot multiply in its presence. Moreover, inclusion of exogenous IL-10 in clonal cultures propagated with IL-2 results in suppression of their growth. These findings, together with the observation that IL-10 fails to protect T cells against activation-induced cell death (a fas/fas-ligand-dependent phenomenon blocked only by certain antagonistic anti-fas reagents), suggest that the negative regulatory effects of IL-10 outweigh the upregulated proliferation observed on some T cell clones (TCC) in the absence of IL-2.