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 k nown for its negative regulatory effects on T cell immunity. It inhibi ts responses indirectly by downregulating expression of major histocom patibility complex (MHC) molecules and co-stimulatory molecules such a s 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 prote ct activated T cells against apoptosis caused by withdrawal of the maj or growth factor, IL-2, and allow proliferation of T cells in the abse nce of IL-2, However, we show here that this IL-10-dependent, IL-2-ind ependent proliferative response is short-lived, and that IL-10-respons ive T cells cannot multiply in its presence, Moreover, inclusion of ex ogenous IL-10 in clonal cultures propagated with IL-2 results in suppr ession of their growth, These findings, together with the observation that IL-10 fails to protect T cells against activation-induced cell de ath (a fas/fas-ligand-dependent phenomenon blocked only by certain ant agonistic anti-fas reagents), suggest that the negative regulatory eff ects of IL-10 outweigh the upregulated proliferation observed on some T cell clones (TCC) in the absence of IL-2.