VSV-primed CD8+ T cells suppress autoreactive germinal centers

Abstract Pathogenic infections are important environmental modifiers of autoimmune disease as they can alter the immune system in a way that either promotes or reduces autoimmune responses. We tested the effect of infection with vesicular stomatitis virus (VSV) on the FcγR2B−/− (R2) mouse strain that spontaneously develops lupus disease. Infecting FcγR2B−/− mice with live VSV reduces autoantibody levels and inflammatory pathology and prolongs survival. We showed that VSV-mediated protection can be transferred in a CD8 cell adoptive transfer experiment. After further testing the transfer of various CD8 T cell subsets, we have identified CD8+CD122+NKG2D+ cells as mediator in VSV-induced Lupus amelioration. RNA Sequencing data for gene expression profiles among various CD8 subsets, indicate that the protective cells express higher level of genes linked to memory phenotype. Our working hypothesis is that the viral infection may induce the expansion of long lived CD8 populations that regulate the antibody response. In support of the idea we initiated to identify the target of the VSV-primed CD8 T cells in vivo. We examined the effect of VSV-primed CD8 T cells on the immune phenotypes of recipient R2 mice at the initial stages, e.g. after 1, 2 or 3 weeks of transfer. Interestingly, we found that Tfh and germinal center B cells are significantly reduced after three weeks of VSV-CD8 transfer. Thus, the protective CD8 T cells from VSV-infected mice might target autoreactive germinal center to regulate the antibody response. How VSV-CD8 T cells might control germinal center & why it takes about 3 weeks for controlling is under investigation.