Relationship between T-Cell responses to CMV, markers of inflammation, and frailty in HIV-uninfected and HIV-infected men in the multicenter AIDS cohort study

Joseph B. Margolick, Jay H. Bream, Tricia L. Nilles, Huifen Li, Susan J. Langan, Shane Deng, Ruibin Wang, Nikolas Wada, Sean X. Leng

Research output: Contribution to journalArticlepeer-review

Abstract

Background Both aging and treated human immunodeficiency virus (HIV)-infected populations exhibit low-level chronic immune activation of unknown etiology, which correlates with morbidity and mortality. Cytomegalovirus (CMV) infection is common in both populations, but its relation to immune activation is unknown. Methods T cells from men who have sex with men (22 virologically suppressed HIV +, 20 HIV -) were stimulated with peptides spanning 19 CMV open reading frames, and intracellular cytokine responses were assessed. Soluble and cellular inflammatory markers were assessed by multiplex electrochemiluminescence and flow cytometry, respectively. Frailty was assessed by the Fried criteria. Results All men had responses to CMV. Proportions of CMV-responsive T cells correlated strongly (r ≥ 0.6 or ≤ -0.6; P <.05) with immunologic markers, depending on donor HIV and frailty status. Markers significantly correlated in some groups after adjustment for multiple comparisons included interferon-3, tumor necrosis factor-α, interleukin-6, and several chemokines in serum, and the proportion of activated T cells. The magnitude of the CD4 IL-2 response significantly predicted onset of frailty in HIV - nonfrail men, but not in HIV + nonfrail men. Conclusions T-cell responses to CMV may strongly influence chronic immune activation in HIV-uninfected and virologically suppressed HIV-infected men, and may predict frailty in HIV-uninfected men.

Original languageEnglish (US)
Pages (from-to)249-258
Number of pages10
JournalJournal of Infectious Diseases
Volume218
Issue number2
DOIs
StatePublished - Jun 20 2018

Keywords

  • HIV infection
  • aging
  • chronic inflammation
  • frailty
  • immune activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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