Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection

Cell Immunol. 2015 Sep;297(1):19-32. doi: 10.1016/j.cellimm.2015.05.005. Epub 2015 May 30.

Abstract

The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.

Keywords: Co-stimulation; HIV/TB co-infection; Immune activation; Immunosenescence; T-cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / biosynthesis
  • Adult
  • CD4-CD8 Ratio
  • CD57 Antigens / biosynthesis
  • CD57 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cellular Senescence / immunology*
  • Coinfection / immunology
  • Disease Progression
  • Female
  • Granzymes / metabolism
  • HIV Infections / immunology*
  • HLA-DR alpha-Chains / immunology
  • Humans
  • Immunosenescence / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-7 Receptor alpha Subunit / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Perforin / metabolism
  • Tuberculosis, Pulmonary / immunology*

Substances

  • CD57 Antigens
  • HLA-DR alpha-Chains
  • Interleukin-7 Receptor alpha Subunit
  • Membrane Glycoproteins
  • Perforin
  • Interferon-gamma
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • Granzymes