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

Academic Article

Abstract

  • Self/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 cell responses. 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.
  • Published In

  • Scientific Reports  Journal
  • Digital Object Identifier (doi)

    Author List

  • Daszkiewicz L; Vázquez-Mateo C; Rackov G; Ballesteros-Tato A; Weber K; Madrigal-Avilés A; Di Pilato M; Fotedar A; Fotedar R; Flores JM
  • Volume

  • 5