title: Potential role of γδ T cell-derived IL-17 in acute cardiac allograft rejection.
abstract: BACKGROUND
  Although αβ T cells are known to participate in the development of acute cardiac allograft rejection, the role of γδ T cells remains poorly understood. We hypothesized that γδ T cells contribute to acute allograft rejection thru interleukin (IL)-17 production.
  
  
  METHODS
  Donor hearts from FVB mice (H-2q) were heterotopically transplanted into C57BL/6-wild type (WT) and γδ T cell-deficient (TCRδ-/-) recipient mice (H-2b). Overall graft survival was monitored. Graft infiltrating cell profile, including γδ T cell subtype, cytokine expression, and myeloperoxidase activity were measured by flow cytometry, TaqMan (Applied Biosystems, Carlsbad, CA) polymerase chain reaction, and myeloperoxidase assay, respectively, on postoperative days 3 and 6.
  
  
  RESULTS
  Graft survival was prolonged in TCRδ-/- recipients compared with WT controls. Graft infiltrating cells, including CD45+, CD4+, CD8+, and Gr1+ cells were significantly decreased in TCRδ-/- recipients compared with WT. Donor hearts transplanted into TCRδ-/- recipients had reduced IL-17 and IL-6 messenger RNA expression. Corroborating the gene expression, intracellular cytokine staining showed decreased IL-17 producing cells in TCRδ-/- recipients. Finally, Vγ1+ and Vγ4+ T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating γδ T cells.
  
  
  CONCLUSIONS
  The γδ T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The γδ T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kimura
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itoh
authors.forename: Denis R
authors.initials: DR
authors.lastname: Merk
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Gong
authors.forename: Homare
authors.initials: H
authors.lastname: Okamura
authors.forename: Paul A
authors.initials: PA
authors.lastname: Chang
authors.forename: Hideo
authors.initials: H
authors.lastname: Adachi
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fischbein
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta