Tu118 - CD4+ T Cells Activated by IMQ Administration in IFNγKO Mice Ameliorate SLE Pathology via Suppression of Antibody-producing Cell Differentiation

Abstract Text: Our previous study revealed that splenic IFNγ+CD4+ T cells were significantly increased after the induction of SLE model by IMQ treatment in C57BL/6 WT mice, thus we evaluated the pathogenic role of IFNγ+CD4+ T cells using IFNγKO (KO) mice. After induction of lupus model by IMQ, KO mice showed lower autoantibody titer and urinary protein, and amelioration of the deposition of immunocomplex in glomeruli compared with WT mice. Although Tfh and Tph cells in spleen showed no significant differences, IL-17+CD4+T cells were significantly increased and IL-10+CD4+ T cells were significantly decreased in KO mice. In addition, plasmablasts were significantly increased and plasma cells tended to be decreased in spleen of KO mice. Co-culture experiments of CD19+ B cells of control mice with CD4+ T cells of WT mice treated with IMQ or control WT mice were performed to evaluate B cell differentiation and IgG production, and revealed that plasmablasts and IgG levels in culture supernatant were significantly increased when using CD4+ T cells of IMQ-treated mice. Moreover, differentiation of age-associated B cells and plasmablasts and IgG levels in culture supernatant were significantly decreased when CD19+ B cells were co-cultured with CD4+ T cells of IMQ-treated KO mice compared with IMQ-treated WT mice. These results suggest that IMQ-induced IFNγ+CD4+ T cells may be involved in autoantibody formation of SLE via enhanced differentiation of antibody-secreting cells.