IL-15 stimulates core 2 O-glycan synthesis and regulates trafficking of memory CD8 T cells during viral skin infection

• DOI: 10.4049/jimmunol.196.supp.119.20
• Publication Date: 2023-01-01T10:24:34Z
• Authors: Jana L Mooster; Jossef Osborn; Tahsin Khan; Jeffrey Nolz
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract Following successful vaccination or pathogen clearance, recently activated CD8+ T cells that survive contraction differentiate into long-lived memory populations and provide host protection against re-infection. We have previously demonstrated that memory CD8+ T cells acquire the capacity to generate core 2 O-glycans in an antigen-independent manner, a post-translational modification required for binding to P- and E-selectin. In addition, we have shown that de novo synthesis of core 2 O-glycans can be regulated by IL-15 signaling and this modulates the ability for memory CD8+ T cells to traffic to inflamed tissues. Herein, we show that the trafficking of memory CD8+ T cells to Vaccinia Virus (VacV)-infected skin occurs in an antigen-independent manner, but that protective immunity requires antigen-specificity. Following epicutaneous infection with VacV, migratory dendritic cells express IL-15Rα, suggesting this cell type could trans-present IL-15 to T cells. In fact, nearly all memory CD8+ T cells in the draining lymph node during VacV infection synthesize core 2 O-glycans regardless of antigen specificity. IL-15 stimulates memory CD8+ T cells to specifically express ST3 beta-galactoside alpha-2,3-sialyltransferase 4 (St3Gal4), an enzyme known to facilitate formation of sialyl Lewis X structures on core 2 O-glycans. Finally, we show that neutralizing IL-15 during VacV infection reduces E-selectin binding by circulating memory CD8+ T cells and results in decreased recruitment of these cells to the infected skin. Overall, these data identify IL-15 and core 2 O-glycan synthesis as critical regulators of memory CD8+ T cell trafficking to viral infection of the skin and perhaps other peripheral tissues.