By B Kyewski
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Extra info for CD4⁺ CD25⁺ regulatory T cells : origin, function and therapeutic potential
Thus, these in vitro data neither strongly support nor exclude the possibility that TR recognize self-antigens with greater avidity than CD25– T cells. Direct characterization of naturally arising TR interactions with selfantigens in vivo has also proven difﬁcult, primarily because for some time the only available readout for TR function in vivo was the prevention of induced or spontaneous pathology. However, it was found independently by several groups that TCR transgenic TR that develop in the presence of the TCR’s cognate peptide ligand encoded by another transgene can proliferate in response to the same neo-self-antigen in vivo (Cozzo et al.
S. Hsieh · A. Y. Rudensky originating from the naturally arising TR population, arguing for an important biological role for regulatory T cells in the down-modulation of immune responses to pathogens. These reports describing reactivity to foreign antigens within the naturally arising TR population appear to be at odds with the prevalent paradigm of TR development commencing upon recognition of high-afﬁnity self-antigens in the thymus. 2 Development of CD25+ regulatory T cells. Potential TCR-ligand interactions that may result in generation of CD25+ T cells with regulatory properties in the thymus (left) and in the periphery (right) The TCR Speciﬁcity of TR 33 development is analogous to conventional CD25– T cell development, except that TR are simply positively selected based on higher-avidity interactions with self-peptide:MHC class II complexes.
28 4 The Paradox of Foreign Antigen Recognition by Regulatory T Cells . . 30 5 TR Appear to Have a Diverse TCR Repertoire That Is Different from the CD25– TCR Repertoire . . . . . . . . . 33 6 A Large Proportion of Peripheral CD25+ TCRs Have Greater Self-Reactivity than CD25– TCRs . . . . . . . . . . 34 7 What Is the Tissue Distribution of TR Target Self-Antigens? . . . . . 36 References . . . . . . . . . . . . . . . . . . . . . . . . . 40 Abstract CD25+ CD4+ T cells (TR ) are a naturally arising subset of regulatory T cells important for the preservation of self-tolerance and the prevention of autoimmunity.