Responses

underpin a significant counter-regulatory mechanism induced by pro-inflamma-tory signals such as interferonγ (IFNγ). Recently, we described cytotoxic CD8+ T-cell reactivity toward IDO both in cancer patients as well as in healthy indi-viduals.1 We showed that the presence of such IDO-specific CD8+ T cells boosts T-cell immunity against viral as well as tumor-associated antigens by eliminating IDO+ suppressive cells, suggesting a role of such effector T cells in the regulation of immune responses. This made us scru-tinize CD4+ IDO-specific T cells. Indeed, the release of pro-inflammatory cytokines by CD4+ IDO-specific T cells may be important as a counter-response to IDO-induced immunosuppression. Hence, we first sat out to analyze if CD4+ T cells nat-urally recognize IDO. In this respect, we frequently observed detectable numbers of IDO-specific CD4+ T cells in cancer patients and, to a lesser extent, in healthy individuals.2 Thus, we identified a Class II-restricted IDO-derived CD4+ T-cell epi-tope in the vicinity of a previously described Class I-restricted IDO-epitope. We found that IDO-specific CD4+ T cells released IFNγ as well as tumor necrosisα (TNFα). The cancer relevance of these CD4+ T cells was further emphasized by the findings that IDO-specific T-cells reacted toward CD4 responses against IDO Mads hald Anderse