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.
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.
Mitsuoka
Naoshi
N
Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata, 700-8558, Japan.
Iwagaki
Hiromi
H
Ozaki
Michitaka
M
Sheng
Sun Dong
SD
Sadamori
Hiroshi
H
Matsukawa
Hiroyoshi
H
Morimoto
Yoshinori
Y
Matsuoka
Junji
J
Tanaka
Noriaki
N
Yagi
Takahito
T
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
D007166:Immunosuppressive Agents; D015847:Interleukin-4; D007371:Interferon-gamma; D016559:Tacrolimus