1. Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection.
- Author
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Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, Sabet NS, Sekaran SD, Ponnampalavanar S, Che KF, Velu V, Kamarulzaman A, Larsson M, and Shankar EM
- Subjects
- ADP-ribosyl Cyclase 1 biosynthesis, Adult, CD4-CD8 Ratio, CD57 Antigens biosynthesis, CD57 Antigens metabolism, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes pathology, Cell Differentiation immunology, Cell Proliferation, Coinfection immunology, Disease Progression, Female, Granzymes metabolism, HLA-DR alpha-Chains immunology, Humans, Interferon-gamma metabolism, Interleukin-7 Receptor alpha Subunit biosynthesis, Lymphocyte Activation immunology, Male, Membrane Glycoproteins biosynthesis, Perforin metabolism, CD8-Positive T-Lymphocytes immunology, Cellular Senescence immunology, HIV Infections immunology, Immunosenescence immunology, Tuberculosis, Pulmonary immunology
- 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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