Impaired IFN-gamma-secreting capacity in mycobacterial antigen-specific CD4 T cells during chronic HIV-1 infection despite long-term HAART

AIDS. 2006 Apr 4;20(6):821-9. doi: 10.1097/01.aids.0000218545.31716.a4.


Objective: To determine whether long-term HAART in chronic HIV-1 infection restores fully functional Mycobacterium tuberculosis (MTB)-specific CD4 T-cell responses.

Design: A cross-sectional study of HIV-1-seropositive subjects on continuous HAART for over one year with CD4 cell counts greater than 300 cells/microl and undetectable viraemia, antiretroviral-naive individuals with primary HIV-1 infection (PHI), and healthy bacillus Calmette-Guérin-vaccinated low-risk controls.

Methods: Purified protein derivative (PPD)-specific cytokine-secreting CD4 T cells were quantified ex vivo by enzyme-linked immunospot assay and intracellular cytokine staining. Lymphoproliferation was detected by [3H]-thymidine incorporation.

Results: PPD-specific IFN-gamma-secreting CD4 T cells were markedly reduced in chronic HAART-treated HIV-1-positive and PHI subjects compared with healthy controls [medians 30, 155 and 582 spot-forming cells/million peripheral blood mononuclear cells (PBMC), respectively, P < 0.0001 and P < 0.002], but the frequency of these cells was, nonetheless, significantly greater in viraemic PHI subjects than in aviraemic chronic HIV-1-positive subjects (P < 0.01). In the latter, low frequencies of PPD-specific IL-2 and IL-4-secreting CD4 T cells were also observed. However, lymphoproliferation was evident after the in-vitro stimulation of PBMC with PPD, indicating that MTB-specific T cells were present. The defect in IFN-gamma secretion could be overcome by culture with IL-12.

Conclusion: Despite an improvement in CD4 T-cell counts after HAART, MTB-specific CD4 T cells from chronically infected patients have impaired IFN-gamma-secreting capacity. The early initiation of HAART might preserve functional CD4 T-cell responses to MTB, and warrants evaluation in populations with a high risk of dual infection.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Chronic Disease
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1*
  • Humans
  • Immune Tolerance / drug effects
  • Interferon-gamma / biosynthesis*
  • Interleukin-12 / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Tuberculin / immunology


  • Anti-HIV Agents
  • Interleukin-2
  • Tuberculin
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma