Balancing respiratory (tissue-resident memory CD8 T cell) T_RM retention and egress

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Presentation Time: 01:15 PM - 01:30 PM
Abstract ID: 5740 - A

Presenting Author:
Taylor N Jones , Graduate Student at Univ. of Rochester Sch. of Med. & Dent.

Abstract:

Influenza virus infection models have demonstrated that site-specific immunological memory acts during early reinfection to prevent disease severity. Most available respiratory virus vaccines don't generate robust tissue-specific memory, which warrants further study. Tissue-resident memory CD8 T cells (T_RM) are a memory T cell (T_m) subset that remain in the tissues and do not recirculate. CD69 is a broad marker of residency and is found on T_RM. Our lab has observed similar pulmonary T_RM identified by integrin CD49a/CD29 expression in both mice and humans. CD49a blockade or CD49a KO in mouse influenza infection models led us to hypothesize that CD49a is important to maintain local lung and airway T_RM. Previously, we have observed redistribution of memory cells from the tissues when CD49a was blocked, leading us to hypothesize that T_RM may possess retention programs that prevent tissue egress and that this is due to the ability of CD49a to bind to collagen IV. S1P1 binds to available S1P to facilitate egress. Through bulk RNA-seq analysis of lung CD8 T_m, we found that cells present in the lungs during the memory phase had negligible S1pr1 expression. S1P1 must be downregulated to prevent egress. However, during early infection, S1P1 is not immediately downregulated upon tissue entry. Interestingly, CD49a is detectable on lung CD8 T cells five days post-infection. We are investigating the relationship between CD49a  and S1P1 to determine what regulates retention.