title: Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins.
abstract: Natural killer T (NKT) cells from mouse and human play an important role in the immune responses against Mycobacterium tuberculosis. However, the function of CD3(+)TCRvβ11(+) NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that after stimulation with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN-γ, TNF-α, IL-2 and IL-17. IL-21-expressing NKT cells in PFMCs displayed effector memory phenotype, expressing CD45RO(high)CD62L(low)CCR7(low). Moreover, NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co-expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD3(+)TCRvβ11(+) NKT cells. Sorted CD3(+)TCRvβ11(+) NKT cells from PFMCs produced IFN-γ and IL-21 after stimulation, which expressed CD40L. Importantly, CD3(+)TCRvβ11(+) NKT cells provided help to B cells for the production of IgG and IgA. Taken together, our data demonstrate that CD3(+)TCRvβ11(+) NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection.
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zitao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Sifei
authors.initials: S
authors.lastname: Yu
authors.affiliation: Chest Hospital of Guangzhou, Guangzhou, China.
authors.forename: Suihua
authors.initials: S
authors.lastname: Lao
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D017252:CD3 Complex / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory; D016130:Immunophenotyping; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D019899:Paracrine Communication; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D054380:Receptors, CXCR5 / Q000276:immunology; D015398:Signal Transduction; D014396:Tuberculosis, Pleural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D000942:Antigens, Bacterial; D017252:CD3 Complex; C095085:CXCR5 protein, human; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054380:Receptors, CXCR5; D023201:CD40 Ligand; D000098546:Interleukin-21
keywords: B cells; IL-21; Immune response; Immunity; Immunology and Microbiology Section; NKT cells; immunoglobulins; tuberculosis