Generation of memory CD4+ T cells after influenza virus infection requires PSGL-1 and selectin binding activity (P6148)

Abstract

Abstract CD4+ memory T cells have a critical role in immunity to new influenza viruses. In particular, lung-resident memory CD4+ T cells are essential for production of innate inflammatory cytokines that promote early virus control. However, the contribution of adhesion molecules in regulating CD4+ T cell memory remains unclear. We assessed the role of PSGL-1, a ligand for the selectin family of adhesion molecules that is highly upregulated on CD4+ T cells during infection. In adoptive transfer studies, we found that PSGL-1 KO CD4+ T cells had increased accumulation in the lungs. However, compared to WT cells, few PSGL-1 KO cells persisted into the memory phase and these cells failed to re-expand upon secondary challenge. When PSGL-1 KO mice were re-challenged with a high dose influenza infection, early virus levels in the lungs were increased and KO mice had prolonged morbibity. To address whether functional selectin binding activity was necessary for the development of memory CD4+ T cell responses we used mice deficient in two α-(1,3)-fucosyltransferases, IV and VII (FuT KO) that generate biologically active PSGL-1. FuT KO CD4+ T cells did not display impaired primary responses in the lymph node but showed altered accumulation in the lungs. Like PSGL-1 KO CD4+ T cells, FuT KO cells failed to re-expand upon secondary challenge. Our findings demonstrate a critical role for PSGL-1 and functionally active selectin ligand generation in the development of effective memory CD4+ T cells.