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- Title
The Role of KLRG1 in Human CD4+ T-Cell Immunity Against Tuberculosis.
- Authors
Zhidong Hu; Hui-Min Zhao; Chun-Ling Li; Xu-Hui Liu; Barkan, Daniel; Lowrie, Douglas B.; Shui-Hua Lu; Xiao-Yong Fan; Hu, Zhidong; Zhao, Hui-Min; Li, Chun-Ling; Liu, Xu-Hui; Lu, Shui-Hua; Fan, Xiao-Yong
- Abstract
<bold>Background: </bold>KLRG1 is a marker of terminally differentiated CD8+ T cells in viral infection, but its role in human Mycobacterium tuberculosis infection remains elusive.<bold>Methods: </bold>A set of cohorts of patients with tuberculosis was designed, and the expression profiles and functions of KLRG1+CD4+ T cells were determined with and without antibody blocking.<bold>Results: </bold>KLRG1 expression on CD4+ T cells was significantly increased in patients with active tuberculosis, compared with healthy controls and patients without tuberculosis. Upon M. tuberculosis-specific stimulation, the ability to secrete interferon γ, interleukin 2, and tumor necrosis factor α was significantly greater in KLRG1-expressing CD4+ T cells than in their KLRG-negative counterparts and was accompanied by a decreased proportion of regulatory T cells and increased Akt signaling. However, KLRG1-expressing CD4+ T cells had a shorter life-span, which was associated with a higher apoptosis rate but a similar proliferative response. Blockade of KLRG1 signaling significantly enhanced interferon γ and interleukin 2 secretion without affecting either cell apoptosis or multiplication. Addition of a specific Akt inhibitor prevented this increased cytokine response, implicating the Akt signaling pathway.<bold>Conclusions: </bold>Our study delineated the profile of KLRG1+CD4+ T cells in patients with tuberculosis and suggests that M. tuberculosis infection drives CD4+ T cells to acquire increased effector function in a terminally differentiated state, which is restrained by KLRG1 via KLRG1/Akt signaling pathway.
- Subjects
KILLER cells; TUBERCULOSIS -- Immunological aspects; IMMUNOCOMPETENT cells; T cells; CD4 antigen
- Publication
Journal of Infectious Diseases, 2018, Vol 217, Issue 9, p1491
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiy046