CD8+ T cell recruitment and memory formation in the nasal mucosa following vaccination 2938

Abstract Description Respiratory pathogens first take their foothold in the nasal mucosa (NM), from which they can replicate, disseminate to the lower airways, and cause life-threating complications. Having a strong line of defense at this primary site of infection can substantially help prevent disease. CD8+ Tissue resident memory (TRM) T cells are important agents of tissue protection. However, current peripheral vaccination strategies do not elicit strong TRM responses in the airways. It is also unclear how CD8+ T cells get recruited to the NM. Here, we outline the necessary molecular signals for effector CD8+ T cell entry into the NM, namely CXCR3 and α4 integrin expression and interaction with endothelium-expressed E and P-selectins. We concurrently describe a vaccination strategy that allows the recruitment of a sizable CD8+ T cell population to the NM that persists into memory relying on CXCR6. Using ovalbumin and poly(I:C) as our vaccine, we create a peripheral priming step which allows an α4-dependent recruitment of a small population of pioneer OT-I cells to the tissue. Five days later, we deliver ovalbumin to the NM, which in turn allows the recruitment of more CD8+ T cells, a step dependent on IFNγ expression from the pioneer cells. Overall, we uncover key recruitment signals for CD8+ T cells entry into the NM, outline a strategy to boost recruitment as well as the establishment of TRMs capable of significantly reducing viral burden following Influenza A virus (IAV) infection. Topic Categories Mucosal and Regional Immunology (MUC)