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Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection
- Source :
- Cellular immunology. 297(1)
- Publication Year :
- 2015
-
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.
- Subjects :
- Adult
Male
Immunosenescence
Immunology
CD4-CD8 Ratio
HIV Infections
HLA-DR alpha-Chains
Biology
CD38
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Granzymes
Interleukin-7 Receptor alpha Subunit
Interferon-gamma
CD57 Antigens
Co-stimulation
Cytotoxic T cell
Humans
Interleukin-7 receptor
Tuberculosis, Pulmonary
Cellular Senescence
Cell Proliferation
Membrane Glycoproteins
Coinfection
Perforin
virus diseases
Cell Differentiation
ADP-ribosyl Cyclase 1
Granzyme B
Disease Progression
Cytokine secretion
Female
CD8
Subjects
Details
- ISSN :
- 10902163
- Volume :
- 297
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cellular immunology
- Accession number :
- edsair.doi.dedup.....fbdd45eba10941be6446e021683e9243