title: Intragraft Vδ1 γδ T cells with a unique T-cell receptor are closely associated with pediatric semiallogeneic liver transplant tolerance.
abstract: BACKGROUND
  T-cell receptor Vδ2 γδ T cells (Vδ2 cells) participate in host defense, whereas Vδ1 γδ T cells (Vδ1 cells) may regulate immune responses. Vδ1 cells appear to play a role in fetomaternal tolerance and our aim was to examine their role in liver transplant tolerance.
  
  
  METHODS
  To determine whether Vδ1 cells increase within accepted grafts after semiallogeneic pediatric liver transplantation, the Vδ1/Vδ2 ratio was assessed at the transcriptional level and the complementarity-determining region 3 loop of the δ chain of Vδ1 cells was sequenced in biopsies from immunosuppression-free (n=6) or almost free (n=3) liver transplant recipients, referred to as group tolerance (Gr-Tol; n=9). The results were compared with biopsies from grafts of recipients on maintenance immunosuppression due to concern of rejection (Gr-IS; n=11). Chronically rejected grafts (Gr-CR; n=6) and normal livers (Gr-NL; n=8) were also examined.
  
  
  RESULTS
  The Vδ1/Vδ2 ratio was the highest in Gr-Tol (0.07±0.06) compared with Gr-IS (0.03±0.02; P=0.04), Gr-CR (0.01±0.02; P=0.008), and Gr-NL (0.02±0.04; P=0.01). There was an identical complementarity-determining region 3 sequence (100% homologous) among all recipients in Gr-Tol, which was dominant in six of nine recipients. This sequence was not seen in Gr-IS or Gr-CR, although it was observed in five of six normal livers.
  
  
  CONCLUSIONS
  A unique Vδ1-bearing T-cell clone accumulates within accepted human liver grafts. It might be useful as a biomarker of tolerance and the identification of its ligand might aid in the development of a novel strategy for tolerance induction.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohe
authors.forename: Hanaa
authors.initials: H
authors.lastname: Nafady-Hego
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: G Alex
authors.initials: GA
authors.lastname: Bishop
authors.forename: Takaaki
authors.initials: T
authors.lastname: Koshiba
mesh_terms: D002648:Child; D002675:Child, Preschool; D022801:Complementarity Determining Regions / Q000737:chemistry; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D022801:Complementarity Determining Regions; D016692:Receptors, Antigen, T-Cell, gamma-delta