title: The impact of portal infusion with donor-derived bone marrow cells and intracellular cytokine expression of graft-infiltrating lymphocytes on the graft survival in rat small bowel transplant model.
abstract: BACKGROUND
  Intraportal administration of alloantigen is reported to reduce antigen-specific immune responses, although the underlying mechanisms for the reduced immunological reactions, especially those of the graft, are poorly understood. We examined intracellular cytokine production by graft-infiltrating lymphocytes (GILs) and peripheral blood lymphocytes (PBLs) to elucidate the underlying mechanisms of beneficial effects on intraportal infusion of donor cells in rat small bowel transplantation (SBT).
  
  
  METHODS
  Recipient rats (Lewis) were transplanted with small bowel from ACI rats. Tacrolimus (Tac) was injected daily from days 0 to 4. Bone marrow cells of ACI rats were infused via the portal or tail vein on the day of surgery. On day 5, both GILs and PBLs collected from SBT graft and peripheral blood, respectively, were analyzed for intracellular cytokine production of recipient-derived alphabeta-T cells. The Th1/Th2 balance in each group was designated as the ratio of the percentage of GILs or PBLs staining positive for intracellular IL-4 or IFN-gamma, respectively. The total cell numbers of GILs from SBT graft were also counted.
  
  
  RESULTS
  Survival of recipients was markedly prolonged by the combination of Tac and donor-specific bone marrow infusion via the portal vein (DSBMI-PV-Tac) compared with the untreated control, Tac alone, or DSBMI tail vein plus Tac. DSBMI-PV-Tac significantly decreased the total cell numbers of GILs and also induced remarkable Th2-type response in GILs.
  
  
  CONCLUSIONS
  Our results indicate that DSBMI-PV-Tac decreased GILs and enhanced Th2-type response in SBT graft, both of which are associated with a significant prolongation of graft survival in SBT.
authors.affiliation: Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata, 700-8558, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Mitsuoka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwagaki
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Sheng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsukawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007421:Intestine, Small / Q000473:pathology / Q000637:transplantation*; D008297:Male; D023421:Models, Animal; D011169:Portal Vein; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D015847:Interleukin-4; D007371:Interferon-gamma; D016559:Tacrolimus