Involvement of CD244 in Regulating CD4+ T Cell Immunity in Patients with Active Tuberculosis |
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Authors: | Bingfen Yang Xinjing Wang Jing Jiang Xiaoxing Cheng |
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Institution: | Division of Research, Institute of Tuberculosis, 309 Hospital, Beijing, China.; St. Jude Children''s Research Hospital, United States of America, |
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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. |
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