Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection

Blood. 2012 Oct 25;120(17):3466-77. doi: 10.1182/blood-2012-04-422550. Epub 2012 Sep 6.

Abstract

Immediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Antibody-Dependent Cell Cytotoxicity / genetics
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Apoptosis
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation
  • Chronic Disease
  • Gene Expression Regulation / immunology*
  • HIV / physiology
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV Infections / pathology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology
  • Time Factors
  • Viral Load

Substances

  • Interleukin-2
  • Receptors, Interleukin-7
  • Interferon-gamma