1996 Fiscal Year Final Research Report Summary
Induction of unresponsiveness using anti-adhesion therapy
| Project/Area Number |
07457252
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
GOTOH Mitsukazu Osaka University, Department of Bioregulation, Associate Professor, 医学部, 助教授 (50162160)
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| Co-Investigator(Kenkyū-buntansha) |
MIYOSHI Hideyuki Osaka University, Department of Surgery II,Medical Staff, 医学部・附属病院, 医員
OHZATO Hiroki Osaka University, Department of Surgery II,Assistant Professor, 医学部, 助手 (10273682)
UMESHITA Koji Osaka University, Department of Surgery II,Assistant Professor, 医学部, 助手 (60252649)
SAKON Masato Osaka University, Department of Surgery II,Lecturer, 医学部, 講師 (40170659)
MONDEN Morito Osaka University, Department of Surgery II,Professor, 医学部, 教授 (00127309)
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| Project Period (FY) |
1995 – 1996
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| Keywords | LFA-1 / ICAM-1 / anti-adhesion therapy / Islet transplantation / xenotransplantation / antigen presentation / rejection / rat to mouse |
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| Research Abstract |
Cellular immune response for antigen presentation was examined in a rat to mouse xenogeneic combination using species-specific monoclonal antiobodies (mAbs) to donor and recipient ICAM-1 and LFA-1 molecules. Although, either mAb had blocking activity in in vitro MLR assays, marked suppression was demonstrated only when anti-donor (rat) ICAM-1 mAb was combined with anti-recipient (mouse) LFA-1 mAb. Likewise, significant prolongation of islet xenograft survival was observed with the similar treatment of mAbs. Thus, 0.05 mg of anti-mouse LFA-1 mAb and anti-rat ICAM-1 mAb given on days 0 and 1 produced a significant prolongation of graft survival over the control, while anti-mouse ICAM-1 mAb when combined with anti-mouse LFA-1 mAb failed to do so. In this strain combination, mouse T cells were able to proliferate in the presence of rat antigen presenting cells (APCs) in a cell number dependent fashion, but not in the presence of mouse APCs. Binding assay showed that LFA-1 molecules on mouse T cells directly bound immobilized rat ICAM-1 molecules. These results suggest that rat ICAM-1 molecules on APCs can interact with mouse LFA-1 molecules on T cells across a species barrier, and that this binding generates the consequent immune responses leading to rejection, and that mAb treatment against these adhesion molecules of a recipient as well as a donor is crucial for induction of unresponsiveness in a xenogeneic transplantation model.
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[Publications] M.Gotoh, H.Ohzato, T.Fukuzaki, Y.Ohta, M.Nishihara, Y.Hasuike, K.Umeshita, M.Sakon, H.Yagita, K.Okumura, M.Miyasaka, M.Monden: "Role of adhesion molecules in islet allo- and xenograft rejection" Transplant.Proc.28(2). 617 (1996)
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