Rv3615c-Specific CD4+ T Cells Express IL-21 To Help B Cells Produce Immunoglobulins in Tuberculosis Pleurisy

Abstract

Rv3615c is a new vaccine candidate in fighting against Mycobacterium tuberculosis (M.tb) in active Tuberculosis (TB). However, the humoral immune response mediated by Rv3615c remains unclear. In the present study, we found that Rv3615cspecific CD4+ T cells produced IL-21, IFN-γ, TNF-α and IL-17A. IL-21-producing CD4+ T cells were predominantly CD69+ T cells, and displayed effector memory phenotype. The majority of Rv3615c-specific IL-21-expresing CD4+ T cells co-expressed IFN-γ and IL-21+IFN-γ+CD4+ T cells exhibited obviously poly functionality, and correlation of IL-21 expression with Th1 but not Th17. Moreover, Rv3615c-specific CD4+ T cells expressed high levels of Tfh markers CD40L, CXCR5 and BCL-6. The frequency of Bcl-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD4+ T cells. Purified CD4+ T cells produced IL-21 after Rv3615c stimulation, which expressed high levels of CD40L. On the other hand, B cells from PFMCs expressed high levels of CD40 and IL-21R. Importantly, Rv3615c-specific CD4+ T cells provided help to B cells for the production of IgG, IgM and IgA. Taken together, our data demonstrate that Rv3615c-specific CD4+ T cells from a local site of M.tb infection produced IL-21 and expressed CD40L, help B cells to secrete immunoglobulins, and may participate in local immune responses against M.tb infection.