Suppressive activities involving T-B and T-T cell interactions are important to maintain immune system homeostasis. Negative control of IgG2a b+ B cells by anti-IgG2a b T cells derived from Igha mice has been well documented. Nevertheless the real contribution of anti-IgG2a b T cells, endogenously matured in Ighb mice, in controlling IgG2a b+ B cell function has never been investigated. We previously generated anti-IgG2a b TCR-transgenic mice and showed that transgenic T cells were not deleted in the thymus and that they were responsible for a complete and chronic IgG2a b suppression. Here we show that T cells expressing high density of anti-IgG2a b TCR were positively selected in the thymus with a higher efficiency in animals expressing IgG2a b , reached peripheral lymphoid organs and negatively controlled IgG2a b serum levels. Moreover, anti-IgG2a b T cells transgenic for the single TCR g chain, thus undergoing normal ยง rearrangements and normal processes of selection, also reached the periphery and suppressed IgG2a b . Interestingly, concentration of IgG2a b in serum inversely correlated with the peripheral frequency of Ig-specific T cells. Finally, T cells able to suppress IgG2a b were obtained from Ighb non-transgenic mice, indicating that anti-+ 2a b T cells are naturally present in the periphery of Ighb animals. We propose that IgG2a bspecific T cells contribute to determine IgG2a b serum levels in Ighb mice.