Certified Professionals

Although negative selection in the thymus and induction of anergy in the periphery have been widely accepted as mechanisms for controlling autoreactivity, much less attention has been devoted to the role of suppressor T cells in mediating dominant immunologic self-tolerance. In 1995, Sakaguchi et al. (1, 2) made the seminal observation that the transfer of CD4 ϩ T cells which had been depleted of the minor subpopulation (10%) of cells that coexpressed the IL-2 receptor (IL-2R) ␣-chain (CD25) to nu/nu recipients induced organ-specific autoimmune disease in the majority of recipients. Cotransfer of CD4 ϩ CD25 ϩ cells with the CD4 ϩ CD25 Ϫ cells prevented the development of disease. The CD4 ϩ CD25 ϩ population was also shown to be solely responsible for the prevention of autoimmunity observed after mice are thymectomized on the third day of life (3). Rapid progress in the analysis of the regulatory function of the CD4 ϩ CD25 ϩ T cell population was made by the development of in vitro model systems that mimicked the function of these cells in vivo (4–6). Although minor differences were observed in the results obtained by the different groups, it is widely accepted that these cells are both hyporesponsive and suppressive. Further studies demonstrated that the CD4 ϩ CD25 ϩ T cells act through an APC-independent mechanism (7, and unpublished observations). Induction of suppressor activity requires that the CD4 ϩ CD25 ϩ cells be activated through their TCR, but once activated , they suppress T cell activation in an antigen-independent manner without a requirement for reactivation through their TCR. Therefore, we proposed (4) that CD4 ϩ CD25 ϩ cells represent a unique lineage of CD4 ϩ T cells that function as " professional suppressor cells. " The publication in this issue of four papers dealing with different aspects of the function of CD4 ϩ CD25 ϩ T cells clearly indicates that they have now received their " professional certification. " CD4 ϩ CD25 ϩ T Cells Are Generated in the Thymus. Saoudi et al. (8) were the first to describe that potent T regulatory (Tr) cells were present in the thymus of the adult rat. PVG rats develop autoimmune diabetes after adult thymectomy and split-dose irradiation. Transfer of CD4 ϩ CD8 Ϫ thymocytes or CD4 ϩ CD45RC Ϫ peripheral T cells prevented the development of disease. Subsequently, CD4 ϩ CD25 ϩ T cells were identified in the mouse thymus …