The Role of KLRG1 in Human CD4+ T-Cell Immunity Against Tuberculosis. (24th January 2018)

• Record Type: Journal Article
• Authors: Hu, Zhidong; Zhao, Hui-Min; Li, Chun-Ling; Liu, Xu-Hui; Barkan, Daniel; Lowrie, Douglas B; Lu, Shui-Hua; Fan, Xiao-Yong
• Is Part Of: Journal of infectious diseases. Volume 217:Number 9(2018)
• Page Start: 1491
• Page End: 1503
• Publication Date: 2018-01-24
• Subjects: Tuberculosis -- chronic infection -- terminal differentiation -- Akt signaling -- KLRG1 -- immunotherapeutic modality; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy046
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: KLRG1 is a marker of terminally differentiated CD8 + T cells in viral infection, but its role in human Mycobacterium tuberculosis infection remains elusive. Methods: 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. Results: 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. Conclusions: 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. Abstract : This study delineated the profile of KLRG1 + CD4 + T cells in patients with tuberculosis and suggests that Mycobacterium 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.