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Title

Distinct p21 requirements for regulating normal and self-reactive T cells through IFN-γ production.

AuthorsDaszkiewicz, L.; Vázquez-Mateo, C.; Ballesteros-Tato, A.; Weber, K.; Madrigal-Avilés, A.; Di Pilato, Mauro; Fotedar, A.; Fotedar, R.; Flores, J.M.; Esteban, M.; Martínez-A, Carlos; Balomenos, Dimitrios
KeywordsT cells
IFN-γ
Issue Date9-Jan-2015
PublisherNature Publishing Group
CitationScientific Reports, 5 : 7691 (2015)
AbstractSelf/non-self discrimination characterizes immunity and allows responses against pathogens but not self-antigens. Understanding the principles that govern this process is essential for designing autoimmunity treatments. p21 is thought to attenuate autoreactivity by limiting T cell expansion. Here, we provide direct evidence for a p21 role in controlling autoimmune T cell autoreactivity without affecting normal T cellresponses. We studied C57BL/6, C57BL/6/lpr and MRL/lpr mice overexpressing p21 in T cells, and showed reduced autoreactivity and lymphadenopathy in C57BL/6/lpr, and reduced mortality in MRL/lpr mice. p21 inhibited effector/memory CD4(+) CD8(+) and CD4(-)CD8(-) lpr T cell accumulation without altering defective lpr apoptosis. This was mediated by a previously non-described p21 function in limiting T cell overactivation and overproduction of IFN-γ, a key lupus cytokine. p21 did not affect normal T cell responses, revealing differential p21 requirements for autoreactive and normal T cell activity regulation. The underlying concept of these findings suggests potential treatments for lupus and autoimmune lymphoproliferative syndrome, without compromising normal immunity.
Publisher version (URL)http://dx.doi.org/10.1038/srep07691.
URIhttp://hdl.handle.net/10261/146524
DOI10.1038/srep07691
E-ISSN2045-2322
Appears in Collections:(CNB) Artículos
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