γδ T cells are involved in acute HIV infection and associated with AIDS progression

PLoS One. 2014 Sep 4;9(9):e106064. doi: 10.1371/journal.pone.0106064. eCollection 2014.

Abstract

Background: Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described.

Methods: Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79) were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21) at month 0, 6, 12 and 18.

Results: In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027) with Vδ2 population reduced (P = 0.002). Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively), while proportion of terminal γδ T cells increased (P = 0.002). γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008), and IFN-γ-producing cells were unaffected (P = 0.115). Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001), which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes.

Conclusions: γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • Acute-Phase Proteins
  • CD4-CD8 Ratio
  • Carrier Proteins / blood
  • Case-Control Studies
  • Disease Progression
  • HIV Infections / blood
  • HIV Infections / immunology*
  • HIV Infections / microbiology
  • Humans
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharides / blood
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / blood
  • Prospective Studies
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocyte Subsets / immunology*

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • lipopolysaccharide-binding protein

Grants and funding

This work was supported by Twelve-five Project for Control and Prevention of Major Infectious Diseases [2012ZX10001-006], National Natural Science Foundation of China [81371332], and Beijing Key Laboratory [BZ0089]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.