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

Naoshi Mitsuoka, Hiromi Iwagaki, Michitaka Ozaki, Sun Dong Sheng, Hiroshi Sadamori, Hiroyoshi Matsukawa, Yoshinori Morimoto, Junji Matsuoka, Noriaki Tanaka, Takahito Yagi

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4 Citations (Scopus)

Abstract

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). 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 αβ-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. 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. 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.

Original languageEnglish
Pages (from-to)155-160
Number of pages6
JournalTransplant Immunology
Volume13
Issue number3
DOIs
Publication statusPublished - Nov 2004

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Keywords

  • Donor-specific bone marrow infusion
  • Intracellular cytokine profile
  • Portal immunization
  • Small bowel transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

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