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CD4+ T cell anergy prevents autoimmunity and generates regulatory T cell precursors

2016; Nature Portfolio; Volume: 17; Issue: 3 Linguagem: Inglês

10.1038/ni.3331

1529-2916

Lokesh A. Kalekar, Shirdi E Schmiel, Sarada L. Nandiwada, Wing Y. Lam, Laura O. Barsness, Na Zhang, Gretta L. Stritesky, Deepali Malhotra, Kristen E. Pauken, Jonathan L. Linehan, M. Gerard O’Sullivan, Brian T. Fife, Kristin A. Hogquist, Marc K. Jenkins, Daniel L. Mueller,

Immunotherapy and Immune Responses

T cell anergy is a well-established phenomenon, but its physiological role is unclear. Mueller and colleagues demonstrate that anergic self-reactive T cells are present at steady state and that these are predisposed to generate peripheral regulatory T cells. The role of anergy, an acquired state of T cell functional unresponsiveness, in natural peripheral tolerance remains unclear. In this study, we found that anergy was selectively induced in fetal antigen–specific maternal CD4+ T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4+ T cells, enriched for self antigen–specific T cell antigen receptors, was also present in healthy hosts. Neuropilin-1 expression in anergic conventional CD4+ T cells was associated with hypomethylation of genes related to thymic regulatory T cells (Treg cells), and this correlated with their ability to differentiate into Foxp3+ Treg cells that suppressed immunopathology. Thus, our data suggest that not only is anergy induction important in preventing autoimmunity but also it generates the precursors for peripheral Treg cell differentiation.