Poor HIV control in HLA-B*27 and B*57/58 noncontrollers is associated with limited number of polyfunctional Gag p24-specific CD8+ T cells

AIDS. 2013 Jan 2;27(1):17-27. doi: 10.1097/QAD.0b013e32835ac0e1.

Abstract

Objectives: Analysis of immune response in HIV controllers, a unique group of infected individuals who are able to control HIV naturally, has provided us a chance to investigate the roles of host immune responses in HIV control.

Design: In this study, the functional quality of HIV Gag p24-specific CD8 T-cell responses was assessed in two groups of clinically distinct, HLA-B*27, HLA-B*57/58-matched individuals, viremic controllers [plasma HIV load (pVL) ≤ 2000 copies/ml) and noncontrollers (pVL >2000 copies/ml) to determine its impacts on natural HIV clinical outcome.

Methods: An ex-vivo interferon (IFN)-γ ELISpot assay was used to screen for each individual's HIV Gag p24-specific T-cell responses. Intracellular cytokine staining assay was used to determine their functional quality (as number of cytokine being produced).

Results: We found that, in contrast to previous studies, all Thai volunteers with HLA-B*5801 were uniformly noncontrollers. Viremic controllers were observed with a significantly larger number of high functional quality p24-specific CD8 T cells than noncontrollers (P < 0.05). This superior quality of responses was observed at both total p24 and epitope-specific level. Moreover, the absolute number of high functional quality Gag p24-specific CD8 T cells was significantly in a negative correlation with pVL (r = -0.6984, P = 0.0006) and also in a positive correlation with CD4 T-cell count (r = 0.5648, P = 0.0095).

Conclusion: We concluded that an adequate number of high functional quality Gag p24-specific CD8 T cells is strongly associated with a natural HIV controller status.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • HIV Core Protein p24 / immunology*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • HLA-B Antigens / metabolism
  • HLA-B27 Antigen / metabolism
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity, Mucosal / genetics
  • Immunity, Mucosal / immunology*
  • Male
  • Middle Aged
  • Viral Load
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • HIV Core Protein p24
  • HLA-B Antigens
  • HLA-B27 Antigen
  • HLA-B57 antigen
  • HLA-B58 antigen
  • gag Gene Products, Human Immunodeficiency Virus