Treg Review

Treg Review - 2005 Nature Publishing Group

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NATURE IMMUNOLOGY VOLUME 6 NUMBER 4 APRIL 2005 331 REGULATORY T CELLS The adaptive immune system of higher vertebrates provides a more effi- cient and specific immune defense against infectious microorganisms than that afforded by the innate immune system. The hallmark of the adaptive immune system is the random generation of antigen recep- tors in developing lymphocyte clones through a process of somatic cell gene rearrangement mediated by the recombination-activating gene recombinase. The essentially unlimited specificities of this anticipatory recognition system provides an efficient counterbalance to the short reproduction cycles and high mutation rates of infectious microorgan- isms. However, the diversity of antigen recognition afforded by the system also poses the threat of autoimmunity because of the generation of self-reactive receptors. Moreover, the emergence of major histocom- patibility complex (MHC)–restricted T cell recognition exacerbates this threat, because to develop, T cells must express antigen receptors that interact with self peptide–MHC complexes. The potential for “horror autotoxicus,” or autoimmunity, was rec- ognized by Paul Ehrlich more than 100 years ago when he noted that a “well adapted regulatory contrivance” must exist to counter this problem 1 . Expanded and developed in the framework of the clonal selection hypothesis, the idea of immunological ‘tolerance’ proposed a requirement for the elimination of autoreactive lymphocyte clones during development 2,3 . A vast body of experimentation over the past half-century has elucidated both cellular and molecular mechanisms leading to deletion or functional inactivation of autoreactive T and B cells in the primary lymphoid organs, thymus and bone marrow, respectively, or in the periphery. Collectively, these mechanisms act in a cell-intrinsic way and are therefore dubbed ‘recessive tolerance’, as elimination of an individual autoreactive lymphocyte clone does not affect other self-reactive clones. Over the past decade a population of so-called ‘regulatory T cells’ (T reg cells) has been linked to the preven- tion of autoimmunity. T reg cells act in a dominant, trans-acting way to actively suppress immune activation, thereby functioning as critical mediators of self-tolerance and immune homeostasis. Accumulating experimental evidence suggests that the immunosuppressive potential of these cells can be harnessed therapeutically to treat autoimmunity and facilitate transplantation tolerance or can be targeted to potentiate tumor immunotherapy. In this review we discuss the principal advances in our understanding of the molecular mechanisms of T reg cell devel- opment and function. We focus on the identification of the forkhead transcription factor Foxp3 as the unique molecular marker of T reg cells and its function as the T reg cell lineage specification factor.
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This note was uploaded on 01/03/2012 for the course BI 144 taught by Professor List during the Fall '10 term at Caltech.

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Treg Review - 2005 Nature Publishing Group

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