CD41CD251 T-cell development is regulated by at least 2 distinct mechanisms

It has recently been shown that CD41CD251 T cells are immunoregulatory T cells that prevent CD41 T-cell–mediated organ-specific autoimmune diseases. In this study, the regulatory mechanism of CD41CD251 T-cell development were investigated using T-cell receptor (TCR) transgenic mice. It was found that CD41CD251 T cells preferentially expressed the endogenous TCRa chain in DO101 TCR transgenic mice compared with CD41CD252 T cells. Moreover, it was found that CD41CD251 thymocytes were severely decreased in DO101 TCR-a2/2 mice in positively selecting and negatively selecting backgrounds, whereas CD41CD252 thymocytes efficiently developed by transgenic TCR in DO101 TCRa2/2 mice in positively selecting backgrounds, indicating that the appropriate affinity of TCR to major histocompatibility complex (MHC) for the development of CD41CD251 thymocytes is different from that of CD41CD252 thymocytes and that a certain TCR–MHC affinity is required for the development of CD41CD251 thymocytes. Finally, it was found that, in contrast to thymus, CD41CD251 T cells were readily detected in spleen of DO101 TCRa2/2 mice in positively selecting backgrounds and that splenic CD41CD251 T cells, but not CD41CD251 thymocytes, were significantly decreased in B-cell– deficient mice, suggesting that B cells may control the peripheral pool of CD41CD251 T cells. Together, these results indicate that the development of CD41CD251 T cells in thymus and the homeostasis of CD41CD251 T cells in periphery are regulated by distinct mechanisms. (Blood. 2002;99:555-560)