Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins

// Changyou Wu 1 , Zitao Li 1 , Xiaoying Fu 1 , Sifei Yu 1 , Suihua Lao 2 and Binyan Yang 1 1 Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China 2 Chest Hospital of Guangzhou, Guangzhou, China Correspondence to: Changyou Wu, email: // Keywords : NKT cells, tuberculosis, IL-21, B cells, immunoglobulins, Immunology and Microbiology Section, Immune response, Immunity Received : July 13, 2015 Accepted : September 05, 2015 Published : September 21, 2015 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.