1995 Fiscal Year Final Research Report Summary
THE IMMUNOLOGICAL HYPORESPONSIVENESS AND DONOR CELL PERSISTENCE IN HOST LIVER AFER PORTAL VENOUS INNOCULATION
| Project/Area Number |
06671205
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Okayama University |
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Principal Investigator |
TANAKA Noriaki Okayama University, Medical School, Associate Professor, 医学部, 助教授 (10127566)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Transplantation / Tolerance / Portal venous / Liver / Kupffer cell |
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| Research Abstract |
The immunosuppressants used now a days in transplantation have not only incomplete inhibition of the rejection but also some incidense of complications such as oppotunistic infection, malignansies etc. hypo- or no response to the antigen is called immunological tolerance, which induces low or no incidense of rejection and results from the reduction of immunosuppressants. Although portal venous inoculation of donor antigen was reported to induce donor-specific hyporesponsiveness and prolongation of the grafts in animal models, the mechanism of the portal tolerance has not been clearly understood. In this study, we investigated the corelation between donor cell persistence in host liver and the suppression of donor-specific mixed lymphocyte reaction. The sequential changes in fluoresence labeled donor cells inoculated via the portal (PV group) or peripheral (IV group) vein were examined using fluoresence microscopy and flow cytometory. The fluorescent positive cells were mainly located i
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n the sinusoid of periportal and midzonal area of hepatic lobules, and several and a few positive cells per hepatic lobules on day 3 and 7, respectively. The number of fluoresent positive cells was seen impresively greater in PV group than in IV group on day 3 and 7. More quantitatively, flow cytometric analysis of the isolated hepatic non-parenchymal cells revealed that the percentage of fluoresent positive cells were significantly higher in PV group than in IV group on day 3, but no significant difference could not be observed between both groups on day 7. MLR was significantly suppressed on day 3 and slightly on day 7 in PV group, comparing with slight MLR suppression only on day 3 in IV group. Gadolinium chloride (Gd) which inhibits the phagocytic activity of Kupffer cell was given intravenously to host rats on 2 consecutive days before portal venous inoculation (GdPV group). In GdPV group high percentage of donor cell persistence and the suppression of MLR by portal venous inoculation were lost to the low level of IV group on day 3. Oral tolerance, which induces the suppression of anbibody production and cellular immunity in an antigen specific fashion, was studied to be able to apply to the transplantation tolerance. Intra-jejunal administration of donor spleen cells (5×10ィイD17ィエD1/day×5days) through the jejunostomy tube was proud to suppress the MLR and foot pad reaction in a donor specific manner, and significantly prolonge the cardiac allograft survival. Gd administration lost these donor-specific immunological hyporesponsiveness and the prolongation of gaft survival. These results indicates that high percentage of persistent donor cells in the host liver was good corelation with the suppression in donor-specific MLR and Kupffer cells play a crucial role in the portal tolerance. Less
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Research Products
(10 results)
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[Publications] Uda, M., Fujiwara, T., Kusaka, S., Matsumoto, T., Tanaka, N., and Orita, K.,: "Donor specific inhibitory factor induced by portal venous inoculation with ultraviolet-B irradiated spleen cells in nonhuman primates."Transplantation Proceedings.. 26. 1848-1850 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakagawa, K., Matsumoto, T., Haisa, M., Fujiwara, T., Isido, N., Tanaka, N., and Orita, K.,: "Induction of MLR hyporesponsiveness after portal venous inoculation with donor splenocytes correlated with persistence of donor lymphocytes in host organs."Transplantation Proceedings.. 28. 1295-1297 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakagawa, K., Matsumoto, T., Haisa, M., Fujiwara, T., Isido, N., Matsuda H, and Tanaka, N.,: "Induction of MLR hyporesponsiveness after portal venous inoculation with donor splenocytes correlated with persistence of donor lymphocytes in host liver."Transplantation Proceedings.. 29. 1139-1140 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishido, N., Matsumoto, T., Matsuoka, J., Nakagawa, K., Haisa, M., Saito, S., Yagi, T., Oishi, M., Ishikawa, T., Fujisawa, K., Matsuda, H., Okada, Y., Endo, A., and Tanaka, N.,: "Can intraoperative inoculation of donor splenocytes via the portal vein prolong allograft survival?"Transplantation Proceedings.. 30. 3883-3884 (1998)
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「研究成果報告書概要(欧文)」より
