Human V?9V?2-T Cells Synergize CD4⁺ T Follicular Helper Cells to Produce Influenza Virus-Specific Antibody.

ABSTRACT: Human V?9V?2-T cells recognize nonpeptidic antigens and exert effector functions against microorganisms and tumors, but little is known about their roles in humoral immune response against influenza virus infection. Herein, in the coculture of autologous human B cells, dendritic cells and/or naïve CD4 T cells, and V?9V?2-T cells, we demonstrated that V?9V?2-T cells could facilitate H9N2 influenza virus-specific IgG and IgM productions in a CD4 T cell-dependent manner. V?9V?2-T cells promoted the differentiation of CXCR5⁺PD1⁺CD4⁺ T follicular helper (Tfh) cells, CD19⁺IgD^-CD38⁺⁺ plasma cells (PCs), and drove B cell proliferation as well as immunoglobulin class switching. Interestingly, V?9V?2-T cells acquired Tfh-associated molecules such as CXCR5, PD1, CD40L, and ICOS during influenza virus stimulation, especially in the presence of CD4 T cells. Moreover, V?9V?2-T cells promoted CD4 T cells to secrete IL-13 and IL-21, and neutralizing IL-13 and IL-21 significantly reduced the number of CD19⁺IgD^-CD38⁺⁺ PCs. Using humanized mice, we further demonstrated that V?9V?2-T cells could synergize CD4 T cells to produce influenza virus-specific antibody. Our findings provide a greater scope for V?9V?2-T cells in adaptive immunity, especially for the Tfh development and humoral immune responses against influenza virus infection.

SUBMITTER: Chen Q 

PROVIDER: S-EPMC5893649 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature