Tissue-resident memory CD8+ T cell development in the upper respiratory tract

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B132
Abstract ID: 5498

Presenting Author:
Kirsten Kost , Graduate Student at Emory Univ. Sch. of Med.

Abstract:

CD8+ tissue-resident memory T cells (TRM) in the upper respiratory tract (URT) limit viral replication and can prevent spread to the lower respiratory tract (LRT), which is the primary cause of morbidity and mortality after respiratory virus infection. Utilizing mouse models, our work explores the interesting dichotomy of URT CD8+ TRM development after intranasal (i.n.) priming, in which localized respiratory antigen is present, and intraperitoneal (i.p.) priming, in which URT CD8+ TRM develop without localized antigen. We explore the early kinetics of TRM formation and demonstrate through bulk RNA sequencing that URT CD8+ memory precursor TRM have unique transcriptional signatures in these distinct infection settings. Using immunofluorescent microscopy, we identify localization of URT CD8+ TRM with and without local antigen. We are currently exploring the role of CD4 T cell help and the respiratory microbiome on the development of URT CD8+ TRM in the presence and absence of local antigen. Additionally, utilizing conditional knockout mouse models, we show that cytokine signals in the URT microenvironment, namely TGF-b and IL-15, drive CD8+ TRM formation in combination with localized antigen. Our work outlines the unique requirements for URT CD8+ TRM formation in the absence of localized respiratory antigen, which can inform T cell-based vaccine strategies against respiratory viruses.