Expression of p16INK4a as a biomarker of T‐cell aging in HIV‐infected patients prior to and during antiretroviral therapy

Aging Cell

Julie A. E. Nelson¹  Janakiraman Krishnamurthy²  Prema Menezes¹  Yan Liu²  Michael G. Hudgens¹  Norman E. Sharpless² 

[1] UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

关键词: human;    immunosenescence;    p16;    T cell;    INK4/ARF;    CDKN2a;   

DOI  :  10.1111/j.1474-9726.2012.00856.x

来源: Wiley

【 摘 要 】

Summary

The p16^INK4a tumor suppressor gene is a mediator of cellular senescence and has been suggested to be a biomarker of ‘molecular’ age in several tissues including T cells. To determine the association of both active and suppressed HIV infection with T-cell aging, T-cell p16^INK4a expression was compared between 60 HIV+ suppressed subjects, 23 HIV+ untreated subjects, and 18 contemporaneously collected HIV-negative controls, as well as 148 HIV-negative historical samples. Expression did not correlate with chronologic age in untreated HIV+ patients, consistent with an effect of active HIV replication on p16^INK4a expression. In patients on cART with suppressed viral loads, however, p16^INK4a levels were similar to uninfected controls and correlated with chronologic age, with a trend toward an inverse correlation with CD4 count. These data show that p16^INK4a is a reliable biomarker of T-cell aging in HIV+ patients with suppressed viral loads and suggest that poor CD4 cell recovery on cART may be associated with increased T-cell expression of p16^INK4a, a marker of cellular senescence.

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland