Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection

PLoS Pathog. 2016 Aug 3;12(8):e1005805. doi: 10.1371/journal.ppat.1005805. eCollection 2016 Aug.

Abstract

The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8+ T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8+ T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8+ T cell perforin expression characteristic of chronic HIV infection.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation*
  • Chronic Disease
  • Female
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • Humans
  • Immunity, Cellular*
  • Male
  • Middle Aged
  • Perforin / immunology
  • T-Box Domain Proteins / immunology

Substances

  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Perforin