| First Author | Gray CC | Year | 2024 |
| Journal | J Leukoc Biol | Volume | 115 |
| Issue | 6 | Pages | 1005-1019 |
| PubMed ID | 38035776 | Mgi Jnum | J:350326 |
| Mgi Id | MGI:7662706 | Doi | 10.1093/jleuko/qiad149 |
| Citation | Gray CC, et al. (2024) VISTA nonredundantly regulates proliferation and CD69low gammadelta T cell accumulation in the intestine in murine sepsis. J Leukoc Biol 115(6):1005-1019 |
| abstractText | Sepsis is a dysregulated systemic immune response to infection i.e. responsible for approximately 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-EF1alpha-GFP-T2A-puro stable Jurkat cell line (Jurkatfoxp3 T cells). Based on our prior study, we investigated the effector cell target of Jurkatfoxp3 T cells in VISTA-/- mice. gammadelta 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 Jurkatfoxp3 T cells nonredundantly modulate the gammadelta T cell population post-CLP. We found that VISTA-/- mice have an increased accumulation of intestinal CD69low gammadelta T cells, which are not protective in murine sepsis. Adoptive transfer of Jurkatfoxp3 T cells decreased the intestinal gammadelta T cell population, suppressed proliferation, skewed remaining gammadelta T cells toward a CD69high phenotype, and increased soluble CD40L in VISTA-/- mice post-CLP. These results support a potential regulatory mechanism by which VISTA skews intestinal gammadelta T cell lineage representation in murine sepsis. |
