摘要 : Sepsis is a dysregulated systemic immune response to infection i.e. responsible for similar to 35% of in-hospital deaths at a significant fiscal healthcare cost. Our laboratory, among others, has demonstrated the efficacy of targe... 展开 Sepsis is a dysregulated systemic immune response to infection i.e. responsible for similar to 35% of in-hospital deaths at a significant fiscal healthcare cost. Our laboratory, among others, has demonstrated the efficacy of targeting negative checkpoint regulators (NCRs) to improve survival in a murine model of sepsis, cecal ligation and puncture (CLP). B7-CD28 superfamily member, V-domain immunoglobulin suppressor of T cell activation (VISTA), is an ideal candidate for strategic targeting in sepsis. VISTA is a 35 to 45 kDa type 1 transmembrane protein with unique biology that sets it apart from all other NCRs. We recently reported that VISTA(-/-) mice had a significant survival deficit post-CLP, which was rescued upon adoptive transfer of a VISTA-expressing pMSCV-mouse Foxp3-EF1 alpha-GFP-T2A-puro stable Jurkat cell line (Jurkat(foxp3) T cells). Based on our prior study, we investigated the effector cell target of Jurkat(foxp3) T cells in VISTA(-/-) mice. gamma delta T cells are a powerful lymphoid subpopulation that require regulatory fine-tuning by regulatory T cells to prevent overt inflammation/pathology. In this study, we hypothesized that Jurkat(foxp3) T cells nonredundantly modulate the gamma delta T cell population post-CLP. We found that VISTA(-/-) mice have an increased accumulation of intestinal CD69(low) gamma delta T cells, which are not protective in murine sepsis. Adoptive transfer of Jurkat(foxp3) T cells decreased the intestinal gamma delta T cell population, suppressed proliferation, skewed remaining gamma delta T cells toward a CD69(high) phenotype, and increased soluble CD40L in VISTA(-/-) mice post-CLP. These results support a potential regulatory mechanism by which VISTA skews intestinal gamma delta T cell lineage representation in murine sepsis. 收起