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

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, Gerard O'Sullivan, Brian T Fife, Kristin A Hogquist, Marc Jenkins, Daniel L Mueller

Research output: Contribution to journalArticlepeer-review

159 Scopus citations


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 (T reg cells), and this correlated with their ability to differentiate into Foxp3 + T reg 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 T reg cell differentiation.

Original languageEnglish (US)
Pages (from-to)304-314
Number of pages11
JournalNature immunology
Issue number3
StatePublished - Feb 1 2016

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© 2016 Nature America, Inc.


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