Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis

PLoS One. 2013 Apr 30;8(4):e63261. doi: 10.1371/journal.pone.0063261. Print 2013.

Abstract

CD244 (2B4) is a member of the signaling lymphocyte activation molecule (SLAM) family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+) T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+) T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M. tuberculosis antigen-specific CD4(+) T cells compared with latent infection individuals. The frequencies of CD244/2B4-expressing antigen-specific CD4(+) T cells were significantly higher in retreatment active TB patients than in new active TB patients. Compared with CD244/2B4-dull and -middle CD4(+) T cells, CD244/2B4-bright CD4(+) T cell subset had significantly reduced expression of IFN-γ, suggesting that CD244/2B4 expression may modulate IFN-γ production in M. tuberculosis antigen-responsive CD4(+) T cells. Activation of CD244/2B4 signaling by cross-linking led to significantly decreased production of IFN-γ. Blockage of CD244/2B4 signaling pathway of T cells from patients with active TB resulted in significantly increased production of IFN-γ, compared with isotype antibody control. In conclusion, CD244/2B4 signaling pathway has an inhibitory role on M. tuberculosis antigen-specific CD4(+) T cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Antigens, CD / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Lymphocyte Activation
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Receptors, Immunologic / analysis
  • Receptors, Immunologic / immunology*
  • Signal Transduction
  • Signaling Lymphocytic Activation Molecule Family
  • Treatment Outcome
  • Tuberculosis / immunology*
  • Tuberculosis / therapy

Substances

  • Antigens, CD
  • CD244 protein, human
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family
  • Interferon-gamma

Grants and funding

The study was supported by grants from National Natural Science Foundation of China (81061120518, 81071318 and 81071319) (http://www.nsfc.gov.cn), by grant for infectious diseases from Ministry of Health and Ministry of Science and Technology, China to XC (2013ZX10003006-003-001) (http://www.moh.gov.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.