@article {217b21ef1c1249948d43ed66e81d800b,
	title = {The role of KLRG1 in human CD4+ T-cell immunity against tuberculosis},
	journal = {Journal of Infectious Diseases},
	volume = {217},
	number = {9},
	year = {2018},
	note = {Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.},
	month = {may},
	pages = {1491{\textendash}1503},
	publisher = {Oxford University Press},
	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{\textendash}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.},
	keywords = {Akt signaling, Chronic infection, Immunotherapeutic modality, KLRG1, Terminal differentiation, tuberculosis},
	issn = {0022-1899},
	doi = {10.1093/infdis/jiy046},
	author = {Zhidong Hu and Zhao, Hui Min and Li, Chun Ling and Liu, Xu Hui and Daniel Barkan and Lowrie, Douglas B. and Lu, Shui Hua and Fan, Xiao Yong}
}
