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

The role that anergy, an acquired state of T cell functional unresponsiveness, plays in natural peripheral tolerance remains unclear. In this study, we demonstrate that anergy is selectively induced in fetal antigen-specific maternal CD4(+) T cells during pregnancy. A naturally occurring subpopulati...

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Detalles Bibliográficos
Autores principales: Kalekar, Lokesh A., Schmiel, Shirdi E., Nandiwada, Sarada L., Lam, Wing Y., Barsness, Laura O., Zhang, Na, Stritesky, Gretta L., Malhotra, Deepali, Pauken, Kristen E., Linehan, Jonathan L., O’Sullivan, M. Gerard, Fife, Brian T., Hogquist, Kristin A., Jenkins, Marc K., Mueller, Daniel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755884/
https://www.ncbi.nlm.nih.gov/pubmed/26829766
http://dx.doi.org/10.1038/ni.3331
Descripción
Sumario:The role that anergy, an acquired state of T cell functional unresponsiveness, plays in natural peripheral tolerance remains unclear. In this study, we demonstrate that anergy is selectively induced in fetal antigen-specific maternal CD4(+) T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4(+) T cells, enriched in self antigen-specific T cell receptors, is also observed in healthy hosts. Neuropilin-1 expression in anergic conventional CD4(+) T cells is associated with thymic regulatory T cell (T(reg) cell)-related gene hypomethylation, and this correlates with their capacity to differentiate into Foxp3(+) T(reg) cells that suppress immunopathology. Thus, our data suggest that not only is anergy induction important in preventing autoimmunity, but it also generates the precursors for peripheral T(reg) cell differentiation.