Expression of p16(INK4a) as a biomarker of T-cell aging in HIV-infected patients prior to and during antiretroviral therapy |
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| Authors: | Nelson Julie A E Krishnamurthy Janakiraman Menezes Prema Liu Yan Hudgens Michael G Sharpless Norman E Eron Joseph J |
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| Institution: | UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Microbiology and Immunology, School of Medicine, 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 Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. |
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| Abstract: | 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. |
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| Keywords: | human immunosenescence p16 T cell INK4/ARF CDKN2a |
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