Tuberculosis specific responses following therapy for TB: Impact of HIV co-infection

Clin Immunol. 2015 Jul;159(1):1-12. doi: 10.1016/j.clim.2015.04.002. Epub 2015 Apr 15.

Abstract

Characterizing perturbations in the immune response to tuberculosis in HIV can develop insights into the pathogenesis of coinfection. HIV+ TB+ and TB monoinfected (TB+) subjects recruited from clinics in Bamako prior to initiation of TB treatment were evaluated at time-points following initiation of therapy. Flow cytometry assessed CD4+/CD8+ T cell subsets and activation markers CD38/HLA-DR. Antigen specific responses to TB proteins were assessed by intracellular cytokine detection and proliferation. HIV+ TB+ subjects had significantly higher markers of immune activation in the CD4+ and CD8+ T cells compared to TB+ subjects. HIV+ TB+ had lower numbers of TB-specific CD4+ T cells at baseline. Plasma IFNγ levels were similar between HIV+ TB+ and TB+ subjects. No differences were observed in in-vitro proliferative capacity to TB antigens between HIV+ TB+ and TB+ subjects. Subjects with HIV+ TB+ coinfection demonstrate in vivo expansion of TB-specific CD4+ T cells. Immunodeficiency associated with CD4+ T cell depletion may be less significant compared to immunosuppression associated with HIV viremia or untreated TB infection.

Keywords: CD4+ T cells; HIV; Tuberculosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antigens, Bacterial / immunology
  • Antitubercular Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Coinfection / drug therapy
  • Coinfection / immunology*
  • Female
  • Flow Cytometry
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HLA-DR Antigens / immunology
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-12 / immunology
  • Interleukin-13 / immunology
  • Interleukin-2 / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-HIV Agents
  • Antigens, Bacterial
  • Antitubercular Agents
  • HLA-DR Antigens
  • IL10 protein, human
  • IL2 protein, human
  • Interleukin-13
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Mycobacterium tuberculosis antigens
  • Interleukin-12
  • Interferon-gamma
  • ADP-ribosyl Cyclase 1