title: Effect of PD-1: PD-L1 in Invariant Natural Killer T-Cell Emigration and Chemotaxis Following Sepsis.
abstract: Invariant natural killer T-cells (iNKT) are a subset of T-cells that play a regulatory role in sepsis. Following cecal ligation and puncture (CLP), iNKT cells emigrate from the liver and into the circulation and peritoneum in a manner dependent upon coinhibitory molecule Programmed Cell Death Receptor 1 (PD-1). We hypothesized that the effect of PD-1 on iNKT-cell emigration was dependent upon the direct PD-1:PD-L1 interaction, and that PD-1 and PD-L1 would play a role in chemotaxis and chemokine receptor expression. Adoptive transfer of Vybrant-labeled wild-type (WT) cells showed the donor iNKT cells migrated from the liver to the peritoneum following CLP, but PD-L1 deficient donor iNKT cells did not. In a chemotaxis assay, WT-iNKT cells chemotaxed to CXCL12, but PD-1 and PD-L1 deficient iNKT cells did not. Using flow cytometry to evaluate chemokine receptor expression, peritoneal iNKT expression of CXCR4 increased following CLP in the WT, PD-1, and PD-L1 deficient animals, and CXCR6 increased in the WT and PD-1 deficient animals. In conclusion here we document that the hepatic emigration of iNKT cells following CLP to the peritoneum appears dependent upon the direct PD-1:PD-L1 interaction; however, although PD-1 and PD-L1 appear to play a role in chemotaxis, this is unlikely a reflection of iNKT-cell chemokine receptor expression changes.
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.
authors.forename: John S
authors.initials: JS
authors.lastname: Young
authors.forename: Daithi S
authors.initials: DS
authors.lastname: Heffernan
authors.forename: Chun-Shiang
authors.initials: CS
authors.lastname: Chung
authors.forename: Maude L
authors.initials: ML
authors.lastname: Kettenmann
authors.forename: Whitney A
authors.initials: WA
authors.lastname: Young
authors.forename: Valeria Sanabria
authors.initials: VS
authors.lastname: Guillen
authors.forename: William G
authors.initials: WG
authors.lastname: Cioffi
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002633:Chemotaxis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D061026:Programmed Cell Death 1 Receptor