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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
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
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2015 (English)In: Cellular Immunology, ISSN 0008-8749, E-ISSN 1090-2163, Vol. 297, no 1, 19-32 p.Article in journal (Refereed) Published
Abstract [en]

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-7R alpha) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-gamma, 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. (C) 2015 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2015. Vol. 297, no 1, 19-32 p.
Keyword [en]
Co-stimulation; HIV/TB co-infection; Immune activation; Immunosenescence; T-cell activation
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-121751DOI: 10.1016/j.cellimm.2015.05.005ISI: 000361173100003PubMedID: 26071876OAI: oai:DiVA.org:liu-121751DiVA: diva2:859349
Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2015-10-06

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Larsson, Marie
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Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
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