HIV-1 infection impairs HSV-specific CD4(+) and CD8(+) T-cell response by reducing Th1 cytokines and CCR5 ligand secretion

J Acquir Immune Defic Syndr. 2011 Sep 1;58(1):9-17. doi: 10.1097/QAI.0b013e318224d0ad.

Abstract

Background: The concept of HIV-1/HSV-negative immunosynergy has recently come to light, which leads us to explore the impact of HIV-1 infection on HSV-specific T-cell immunity.

Methods: : A combination of interferon (IFN)-γ ELISpot and Luminex-based multicytokine profiling assays was used to compare, in a cross-sectional study, the HSV-specific CD4 and CD8 T-cell responses between 20 HIV-1/HSV-coinfected and 12 HIV-1-uninfected/HSV-infected individuals after in vitro restimulation with HSV glycoprotein D (gD) peptide epitopes.

Results: In response to CD4 and CD8 gD peptide epitopes, mean value (±standard errors of the mean) of the different IFN-γ-secreting T cells (ISC) means was significantly reduced in HIV-1/HSV-coinfected individuals (70 ISC ± 10 and 60 ISC ± 8/10 cells) compared with HIV-1-uninfected/HSV-infected individuals (280 ISC ± 25 and 234 ISC ± 23/10 cells, both P < 0.001). After stimulation with the immunodominant CD4 gD and CD8 gD peptide epitopes, the Th1 cytokine and CCR5 ligand secretions were decreased in the HIV-1-infected group although Th17 cytokines increased. The mean concentration of interleukin (IL)-2, IFN-γ, the IFN-γ-induced protein 10 kDa, and the monokine induced by IFN-γ was correlated to the mean concentration of macrophage inflammatory proteins (MIP-1α, MIP-1β), RANTES and Eotaxin (ρ = 0.56, P = 0.02 and ρ = 0.52, P = 0.03).

Conclusions: HIV-1 infection impairs both the number and function of HSV-specific T cells. The downregulation of Th1 cytokines and CCR5 ligands in HIV-1/HSV-coinfected individuals may further facilitate both HSV reactivations and HIV-1 replication.

Publication types

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

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology*
  • Cytokines / metabolism*
  • Down-Regulation
  • Epitopes / immunology
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1*
  • Herpes Simplex / complications
  • Herpes Simplex / immunology
  • Humans
  • Ligands
  • Male
  • Middle Aged
  • Receptors, CCR5 / metabolism
  • Simplexvirus / immunology*
  • Th1 Cells / immunology
  • Viral Proteins / immunology

Substances

  • Cytokines
  • Epitopes
  • Ligands
  • Receptors, CCR5
  • Viral Proteins