Details

Autor(en) / Beteiligte

• Daszkiewicz, Lidia
• Vázquez-mateo, Cristina
• Rackov, Gorjana
• Ballesteros-tato, André
• Weber, Kathrin
• Madrigal-avilés, Adrián
• Di Pilato, Mauro
• Fotedar, Arun
• Fotedar, Rati
• Flores, Juana M
• Esteban, Mariano
• Martínez-a, Carlos
• Balomenos, Dimitrios

Titel

Distinct p21 requirements for regulating normal and self-reactive T cells through IFN-[gamma] production

Ist Teil von

• Scientific reports, 2015-01, Vol.5, p.7691

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2015

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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.