title: Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis.
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.
authors: Division of Research, Institute of Tuberculosis, 309 Hospital, Beijing, China.
authors: Bingfen
authors: B
authors: Yang
authors: Xinjing
authors: X
authors: Wang
authors: Jing
authors: J
authors: Jiang
authors: Xiaoxing
authors: X
authors: Cheng
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology*; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology* / Q000628:therapy
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D007371:Interferon-gamma
references: J Immunol. 1999 May 1;162(9):5407-16
references: 10228018
references: PLoS Pathog. 2011 May;7(5):e1002045
references: 21625589
references: Annu Rev Immunol. 2011;29:665-705
references: 21219180
references: Nat Rev Immunol. 2008 Apr;8(4):247-58
references: 18323851
references: J Exp Med. 1993 Oct 1;178(4):1397-406
references: 8376943
references: Crit Rev Immunol. 2006;26(4):317-52
references: 17073557
references: J Infect. 2011 Apr;62(4):292-300
references: 21382414
references: Immunol Rev. 2008 Oct;225:284-99
references: 18837789
references: Eur J Immunol. 2010 Aug;40(8):2139-42
references: 20853500
references: J Immunol. 2008 Jun 15;180(12):8159-67
references: 18523281
references: Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13402-7
references: 20624978
references: Microbes Infect. 2008 Jul;10(9):995-1004
references: 18762264
references: Clin Diagn Lab Immunol. 2005 Jan;12(1):101-6
references: 15642992
references: PLoS Biol. 2010 Jun 29;8(6):e1000407
references: 20613858
references: PLoS Pathog. 2009 Dec;5(12):e1000682
references: 19997502
references: Annu Rev Pathol. 2012;7:353-84
references: 22054143
references: J Clin Invest. 2009 May;119(5):1167-77
references: 19381021
references: Lancet Infect Dis. 2004 Dec;4(12):739-49
references: 15567123
references: J Exp Med. 2004 May 3;199(9):1245-54
references: 15123744
references: Annu Rev Immunol. 2004;22:599-623
references: 15032590
references: Nat Immunol. 2009 Jan;10(1):29-37
references: 19043418
references: Immunity. 2009 Aug 21;31(2):309-20
references: 19664943
references: J Infect Dis. 2011 Nov 15;204 Suppl 4:S1120-9
references: 21996694
references: Blood. 2005 Jun 15;105(12):4722-9
references: 15713798
references: Nat Med. 2011 Mar;17(3):372-6
references: 21336285
references: J Immunol. 2008 Jul 1;181(1):116-25
references: 18566376
references: Hepatology. 2010 Dec;52(6):1934-47
references: 21064032
references: PLoS One. 2011;6(8):e23700
references: 21887301
references: J Immunol. 1993 Jul 1;151(1):60-70
references: 8326140
references: Immunity. 2011 Aug 26;35(2):285-98
references: 21856186
references: Mol Immunol. 2000 Jun;37(9):493-501
references: 11163399
references: J Immunol. 2005 Jan 15;174(2):800-7
references: 15634901
references: Curr Opin Immunol. 2005 Aug;17(4):374-80
references: 15963709
references: Tissue Antigens. 2004 Aug;64(2):132-44
references: 15245368
references: Eur J Immunol. 2010 Aug;40(8):2211-20
references: 20540114
references: J Exp Med. 2008 Nov 24;205(12):2763-79
references: 19001139