CD28 Agonism Improves Survival in Immunologically Experienced Septic Mice via IL-10 Released by Foxp3⁺ Regulatory T Cells.

ABSTRACT: Immune dysregulation during sepsis is mediated by an imbalance of T cell costimulatory and coinhibitory signaling. CD28 is downregulated during sepsis and is significantly altered on memory versus naive T cells. Thus, to study the role of CD28 during sepsis in a more physiologically relevant context, we developed a "memory mouse" model in which animals are subjected to pathogen infections to generate immunologic memory, followed by sepsis induction via cecal ligation and puncture. Using this system, we show that agonistic anti-CD28 treatment resulted in worsened survival in naive septic animals but conferred a significant survival advantage in immunologically experienced septic animals. Mechanistically, this differential response was driven by the ability of CD28 agonism to elicit IL-10 pr

SUBMITTER: Sun Y 

PROVIDER: S-EPMC7725929 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature