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. 2017 Aug 14;12(8):e0183357.
doi: 10.1371/journal.pone.0183357. eCollection 2017.

Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls

Thijs Booiman  1   2 , Ferdinand W Wit  2   3   4 , Arginell F Girigorie  1   2 , Irma Maurer  1 , Davide De Francesco  5 , Caroline A Sabin  5 , Agnes M Harskamp  1 , Maria Prins  6 , Claudio Franceschi  7 , Steven G Deeks  8 , Alan Winston  9 , Peter Reiss  2   3   4 , Neeltje A Kootstra  1 ; Co-morBidity in Relation to Aids (COBRA) Collaboration
Affiliations

Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls

Thijs Booiman et al. PLoS One. .

Abstract

HIV-1-positive individuals on successful antiretroviral therapy (ART) are reported to have higher rates of age-associated non-communicable comorbidities (AANCCs). HIV-associated immune dysfunction has been suggested to contribute to increased AANCC risk. Here we performed a cross-sectional immune phenotype analysis of T cells in ART-treated HIV-1-positive individuals with undetectable vireamia (HIV-positives) and HIV-1-negative individuals (HIV-negatives) over 45 years of age. In addition, two control groups were studied: HIV negative adults selected based on lifestyle and demographic factors (Co-morBidity in Relation to AIDS, or COBRA) and unselected age-matched donors from a blood bank. Despite long-term ART (median of 12.2 years), HIV-infected adults had lower CD4+ T-cell counts and higher CD8+ T-cell counts compared to well-matched HIV-negative COBRA participants. The proportion of CD38+HLA-DR+ and PD-1+ CD4+ T-cells was higher in HIV-positive cohort compared to the two HIV-negative cohorts. The proportion CD57+ and CD27-CD28- cells of both CD4+ and CD8+ T-cells in HIV-positives was higher compared to unselected adults (blood bank) as reported before but this difference was not apparent in comparison with well-matched HIV-negative COBRA participants. Multiple regression analysis showed that the presence of an increased proportion of terminally differentiated T cells was strongly associated with CMV infection. Compared to appropriately selected HIV-negative controls, HIV-positive individuals on ART with long-term suppressed viraemia exhibited incomplete immune recovery and increased immune activation/exhaustion. CMV infection rather than treated HIV infection appears to have more consistent effects on measures of terminal differentiation of T cells.

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Conflict of interest statement

Competing Interests: F. W. N. M. W. has received travel grants from Gilead Sciences, ViiV Healthcare, Boehringer Ingelheim, Abbvie, and Bristol-Myers Squibb. A.W. has received honoraria or research grants from or been a consultant or investigator in clinical trials sponsored by Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Roche, Pfizer and ViiV Healthcare. P. R., through his institution, received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals, Merck, Bristol-Myers Squibb, and ViiV Healthcare; served on a scientific advisory board for Gilead Sciences and a data safety monitoring committee for Janssen Pharmaceuticals; and chaired a scientific symposium by ViiV Healthcare, for which his institution has received remuneration. The other authors report no conflicts of interest exist.We confirm that the statement does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. CD4 and CD8 T cell activation and exhaustion in HIV-positive and HIV-negative COBRA participants, and blood bank donors.
(a) The percentage of activated (HLA-DR+CD38+) and (b) exhausted (PD-1+) CD4+ T cells within the CD4+ T-cell population. (c) The percentage of activated (HLA-DR+CD38+) and (d) exhausted (PD-1+) T cells within the CD8+ T-cell population. Significance was assessed with multivariable linear regression, corrected for age and gender. HIV+, HIV-positive; HIV-, HIV-negative; BBD, blood bank donors.
Fig 2
Fig 2. Terminally differentiated CD4 and CD8 T cells in HIV-positive and HIV-negative COBRA participants, and blood bank donors.
(a) The percentage of CD57+ and CD27−CD28− T cells within the CD4+ T cell population. (b) The percentage of CD57+ and CD27−CD28− T cells within the CD8+ T cell population. (c) The percentage of CD57+ cells in the CD4+CD28− and (d) CD8+CD28−cell population. Significance was assessed with multivariable linear regression, corrected for age and gender. HIV+, HIV-positive; HIV-, HIV-negative; BBD, blood bank donors.
See this image and copyright information in PMC

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