Anti-TIGIT differentially affects sepsis survival in immunologically experienced versus previously naive hosts.

ABSTRACT: Mounting evidence suggests that the balance of T cell costimulatory and coinhibitory signals contributes to mortality during sepsis. Here, we identified a critical role of the coinhibitory molecule T cell Ig and ITIM domain (TIGIT) in regulating sepsis mortality. Because TIGIT is significantly upregulated on memory T cells, we developed a "memory mouse" model to study the role of TIGIT during sepsis in a more physiologically relevant context. Mice received sequential pathogen exposure and developed memory T cell frequencies, similar to those observed in adult humans, and were then subjected to sepsis induction via cecal ligation and puncture. Our results show that targeting the TIGIT pathway during sepsis is fundamentally different in previously naive versus memory mice, in that αTIGIT Ab

SUBMITTER: Sun Y 

PROVIDER: S-EPMC8021109 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature