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Keywords:

  • human;
  • immunosenescence;
  • p16;
  • T cell;
  • INK4/ARF;
  • CDKN2a

Summary

The p16INK4a 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 p16INK4a 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 p16INK4a expression. In patients on cART with suppressed viral loads, however, p16INK4a 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 p16INK4a 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 p16INK4a, a marker of cellular senescence.