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Self-Tolerance: Multiple Strategies For Peripheral Unresponsiveness Of T Cells
Published 1997 · Biology
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We discuss in this paper various strategies taken by the immune system to achieve and maintain the self-tolerance. Using transgenic mice with TcR s and s chain genes from a CD4 dependent self class II-reactive TH2 cell clone, we demonstrated that T cells expressing self-reactive TcR are not deleted in the thymus but are positively selected and released into the peripheral lymphoid pool. Transgenic mice with a large number of autoreactive T cells did not show any signs of autoimmunity and survived normally in specific pathogen free (SPF) conditions. The cells were, however, found not to be anergic, and fully retained the self class II reactivity in vitro to produce interleukins. Various degrees of down regulation of CD2 and costimulatory and cell surface marker molecules were detected. Upon stimulation in vivo, the autoreactive cells responded to downregulate the surface TcR of their own and inhibited the up regulation of class II antigen on antigen-presenting cells (APC). These results indicate that autoreactive T cells are rendered tolerant by diverse mechanisms rather than by simple clonal deletion and anergy.