Inhibitory and stimulatory effects of IL-10 on human CD8(+) T cells

IL-10 is a well-documented immunosuppressant that inhibits macrophage-dependent Ag presentation and CD4(+) T cell proliferation in vitro. We report that IL-10 inhibits alloantigen-specific proliferative responses and induces a long lasting anergic state in human purified CD8(+) T cells when added concomitantly with the Ag in the presence of APC. Moreover, the generation of allospecific cytotoxic activity is inhibited by IL-10, These effects are indirect and are mediated through inhibition of the costimulatory functions of APC. In contrast, IL-10 has no direct inhibitory effects on the proliferation of purified CD8(+) T cells activated by anti-CD3 mAb and promotes the growth of activated CD8(+) T cells in combination with low doses of IL-2. Taken together, these results indicate that IL-10 has differential effects on CD8(+) T cells depending on their state of activation, which may explain both the enhancing and inhibitory effects observed after IL-10 treatment in different in vivo experimental models.