Antigen-Induced IL-10+ Regulatory T Cells Are Independent of CD25+ Regulatory Cells for Their Growth, Differentiation, and Function1

Recent studies have emphasized the importance of T cells with regulatory/suppressor properties in controlling autoimmune diseases. A number of different types of regulatory T cells have been described with the best characterized being the CD25 + population. In addition, it has been shown that regulatory T cells can be induced by specific Ag administration. In this study, we investigate the relationship between peptide-induced, CD4 + regulatory T cells and naturally occurring CD4 + CD25 + cells derived from the Tg4 TCR-transgenic mouse. Peptide-induced cells were FoxP3 − and responded to Ag by secreting IL-10, whereas CD25 + cells failed to secrete this cytokine. Both cell types were able to suppress the proliferation of naive lymphocytes in vitro although with distinct activation sensitivities. Depletion of CD25 + cells did not affect the suppressive properties of peptide-induced regulators. Furthermore, peptide-induced regulatory/suppressor T cells could be generated in RAG −/− , TCR-transgenic mice that do not spontaneously generate CD25 + regulatory cells. These results demonstrate that these natural and induced regulatory cells fall into distinct subsets.