Expression and function of NKG2D is impaired in CD8+ T cells of chronically HIV-1-infected patients without ART

Erica Giuliani, Lia Vassena, Maria Giovanna Desimio, Anna Rita Buonomini, Vincenzo Malagnino, Massimo Andreoni, Margherita Doria

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Increasing line of evidence indicates that the NKG2Dactivating receptor plays a relevant role in the effector functions of cytotoxic lymphocytes. In this study, we investigated the expression and function of NKG2D in CD8+ T cells from chronically HIV-1- infected patients with or without antiretroviral therapy (ART). Methods: We measured by flow cytometry the expression of NKG2D on CD8+ T-cell subsets of ART-naive and ART patients as well as seronegative healthy subjects (HIV-neg). An intrapatient analysis before and after ART initiation was also performed. Results were correlated with viral load, CD4+ T-cell counts, markers of immune activation (CD38, sCD14), and soluble NKG2D ligands (sMICA and sULBP2). The function of NKG2D on CD8+ T cell cytotoxicity was tested by ex vivo degranulation assays. Results: We showed that NKG2D was downregulated on all CD8+ T-cell subsets of ART-naive patients. The expression of NKG2D on CD8+ T cells inversely correlated with viral load and CD38 expression but not with plasma levels of sMICA and sULBP2. Importantly, we found that NKG2D-mediated costimulation of CD8+ T-cell lytic activity was strongly reduced in ART-naive patients if compared with HIV-neg and ART subjects. Finally, intrapatient analysis demonstrated that effective anti-HIV-1 therapy restores NKG2D expression and NKG2D-induced cytotoxicity by CD8+ T cells. Conclusions: These data underscore that NKG2D downregulation contributes to impaired CD8+ T-cell responses in untreated HIV-1 infection and have implications for monitoring immune functions and response to treatments, and for the development of novel anti- HIV-1 strategies combining ART with drugs that stimulate NKG2D expression and function.

Original languageEnglish
Pages (from-to)347-356
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume70
Issue number4
Publication statusPublished - Dec 1 2015

Keywords

  • Antiretroviral therapy
  • CD38
  • CD8 T-cell cytotoxicity
  • HIV-1
  • NKG2D

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)

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