CD22 displays CD4+ T cell-intrinsic suppressive functions during a persistent virus infection 2710

Abstract Description Chronic virus infections evade or suppress the host immunity, posing risks to global human health. Lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl 13) infection of mice has been instrumental for defining the mechanisms of viral immune regulation. Sphingosine kinase 2 (SphK2) is an enzyme that mediates the metabolism of bioactive sphingolipids. We demonstrated that SphK2 represses CD4+ T cell immunity during LCMV Cl 13 infection while limiting viral immune pathology. RNA-sequencing analysis revealed that SphK2 controlled CD22 in CD4+ T cells during infection. Indeed, CD22 was significantly upregulated on virus-specific T cells from wild type (WT) mice when compared to SphK2 KO mice upon Cl 13 infection. Upregulation of CD22 was sustained during persistent Cl 13 infection. While transient depletion of CD22 modestly enhanced virus-specific T cell responses, complete deletion of CD22 did not significantly affect T cell immunity or LCMV clearance, suggesting the presence of a compensatory mechanism. Adoptively transferred CD22-deficient TCR transgenic LCMV-specific CD4+ T cells expanded more effectively and exhibited improved functionality compared to their WT CD4+ T cell counterparts upon infection. The results indicate that CD22 has a CD4+ T cell-intrinsic suppressive function during infection. The newly defined SphK2-CD22 axis during T cell immunity to LCMV infection may advance our understanding of virus-instigated immune suppression and viral persistence. Funding Sources Supported by NIH/NIAID R01AI153076 and R01AI162631. Topic Categories Viral Immunology (VIR)