J Immunol. 2026 Jul 10;215(7):vkag183. doi: 10.1093/jimmun/vkag183.
ABSTRACT
Chronic viral infections evade or suppress host immunity, posing risks to global human health. However, the underlying mechanisms of viral immune suppression are incompletely defined. Previously, we have demonstrated that sphingosine kinase 2 (SphK2) represses CD4+ T-cell immunity during lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl 13) infection. Here, our study indicates that CD22 is significantly upregulated on virus-specific T cells, which is largely dependent on SphK2, upon LCMV infection. The upregulation of CD22 on virus-specific T cells is sustained during persistent LCMV Cl 13 infection. While transient depletion of CD22 modestly enhances LCMV-specific T-cell responses, complete deletion of CD22 does not significantly affect T-cell immunity, suggesting the presence of a compensatory mechanism. Adoptively transferred CD22-deficient T-cell receptor transgenic LCMV-specific CD4+ T cells expand more effectively and exhibit improved functionality compared to CD22-sufficient T-cell counterparts. The results indicate that CD22 has a CD4+ T cell-intrinsic suppressive function during infection. Analysis of gene signature profiling further supports the regulatory role of CD22 in LCMV-specific CD4+ T cells. Collectively, the SphK2-CD22 axis during CD4+ T-cell immunity to infection could advance our understanding of virus-instigated immune suppression and viral persistence.
PMID:42433041 | DOI:10.1093/jimmun/vkag183