IMMUNOBIOLOGY CD41 and CD81 anergic T cells induced by interleukin-10–treated human dendritic cells display antigen-specific suppressor activity

Interleukin-10 (IL-10)–treated dendritic cells (DCs) induce an alloantigenor peptide-specific anergy in various CD41 and CD81 T-cell populations. In the present study, we analyzed whether these anergic T cells are able to regulate antigenspecific immunity. Coculture experiments revealed that alloantigen-specific anergic CD41 and CD81 T cells suppressed proliferation of syngeneic T cells in a dosedependent manner. The same effect was observed when the hemagglutininspecific CD41 T-cell clone HA1.7 or tyrosinase-specific CD81 T cells were cocultured with anergic T cells of the same specificity. Anergic T cells did not induce an antigen-independent bystander inhibition. Suppression was dependent on cellto-cell contact between anergic and responder T cells, required activation by antigen-loaded DCs, and was not mediated by supernatants of anergic T cells. Furthermore, anergic T cells displayed an increased extracellular and intracellular expression of cytotoxic T-lymphocye antigen (CTLA)–4 molecules, and blocking of the CTLA-4 pathway restored the T-cell proliferation up to 70%, indicating an important role of the CTLA-4 molecule in the suppressor activity of anergic T cells. Taken together, our experiments demonstrate that anergic T cells induced by IL-10–treated DCs are able to suppress activation and function of T cells in an antigen-specific manner. Induction of anergic T cells might be exploited therapeutically for suppression of cellular immune responses in allergic or autoimmune diseases with identified (auto) antigens. (Blood. 2002;99:2468-2476)