The role of KLRG1 in human CD4+ T-cell immunity against tuberculosis

Zhidong Hu, Hui Min Zhao, Chun Ling Li, Xu Hui Liu, Daniel Barkan, Douglas B. Lowrie, Shui Hua Lu, Xiao Yong Fan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1491-1503
Number of pages13
JournalJournal of Infectious Diseases
Volume217
Issue number9
DOIs
StatePublished - 1 May 2018

Bibliographical note

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Keywords

  • Akt signaling
  • Chronic infection
  • Immunotherapeutic modality
  • KLRG1
  • Terminal differentiation
  • Tuberculosis

Fingerprint

Dive into the research topics of 'The role of KLRG1 in human CD4+ T-cell immunity against tuberculosis'. Together they form a unique fingerprint.

Cite this