title: Interleukin-17-producing CD4(+) cells home to the graft early after human heart transplantation.
abstract: BACKGROUND
  Interleukin-17 (IL-17) is regarded as a major effector cytokine with pro-inflammatory actions. It has pleiotropic and environment-specific functions by promoting adaptive cytotoxic T-lymphocyte responses during inflammation. Therefore, it is tempting to speculate that IL-17 plays a major role in inflammatory responses in transplant recipients. We questioned whether IL-17 is expressed in the transplanted heart during acute rejection (AR), or during immunologic quiescence, and which graft-infiltrating lymphocytes produce IL-17. In addition, we analyzed donor-specific IL-17-producing cells in peripheral blood cells in comparable periods after transplantation.
  
  
  METHODS
  Endomyocardial biopsies from heart transplant recipients with early or late AR or in an immunologic quiescence period were analyzed for the presence of IL-17 mRNA. In addition, the capacity of graft-infiltrating lymphocytes (GILs) to produce IL-17 was analyzed. Moreover, we determined the frequency of donor-reactive IL-17-producing peripheral blood mononuclear cells (PBMCs) using an Elispot assay.
  
  
  RESULTS
  Twenty-one percent (14 of 67) of the biopsies assessed were positive for IL-17 mRNA. Thirteen of 41 biopsies were observed in the early period (≤3 months) after transplantation. One (of 26) of the late biopsies expressed IL-17 (p = 0.006). Specifically, IL-17 was expressed during early AR (57%, or 8 of 14), whereas biopsies from late AR (0 of 5) did not express IL-17 mRNA (p = 0.02). During AR, IL-17 is derived from IL-17-producing CD4(+)CD161(+), and not CD8(+), GILs. In contrast to the graft findings, we detected circulating donor-reactive IL-17-producing cells mostly during immunologic quiescence.
  
  
  CONCLUSIONS
  Particularly early after heart transplantation, IL-17-producing CD4(+) T cells home to the graft, which contributes to the AR process.
authors: Department of (a)Internal Medicine-Transplantation. Electronic address: n.vanbesouw@erasmusmc.nl.
authors: Nicole M
authors: NM
authors: van Besouw
authors: Cardiology.
authors: Kadir
authors: K
authors: Caliskan
authors: Department of (a)Internal Medicine-Transplantation.
authors: Annemiek M A
authors: AM
authors: Peeters
authors: Department of (a)Internal Medicine-Transplantation.
authors: Mariska
authors: M
authors: Klepper
authors: Department of (a)Internal Medicine-Transplantation.
authors: Marjolein
authors: M
authors: Dieterich
authors: Department of Thoracic Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Lex P W M
authors: LP
authors: Maat
authors: Department of (a)Internal Medicine-Transplantation.
authors: Willem
authors: W
authors: Weimar
authors: Cardiology.
authors: Olivier C
authors: OC
authors: Manintveld
authors: Department of (a)Internal Medicine-Transplantation.
authors: Carla C
authors: CC
authors: Baan
mesh_terms: D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D058501:Enzyme-Linked Immunospot Assay; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014184:Transplantation, Homologous
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D012333:RNA, Messenger
keywords: CD161; Elispot; Th17; human; intragraft