The Role of KLRG1 in Human CD4 T-Cell Immunity Against Tuberculosis.

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

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.

KILLER cells; TUBERCULOSIS -- Immunological aspects; IMMUNOCOMPETENT cells; T cells; CD4 antigen

Journal of Infectious Diseases, 2018, Vol 217, Issue 9, p1491

0022-1899

Academic Journal

10.1093/infdis/jiy046