IL-15 stimulates core 2 O-glycan synthesis and regulates trafficking of memory CD8 T cells during viral skin infection
| Autor: | Jana L Mooster, Jossef Osborn, Tahsin Khan, Jeffrey Nolz |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 196:119.20-119.20 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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