1998 Fiscal Year Final Research Report Summary
Tolerance induction by selective inoculation of doner lymphocytes
| Project/Area Number |
08671380
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Nara Medical University |
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Principal Investigator |
HISANAGA Michiyoshi Nara Medical University, Faculty of Medicine, Associate Professor, 医学部, 講師 (30275341)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Hiroshige Nara Medical University, Faculty of Medicine, Professor, 医学部, 教授 (20075071)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Heart transplantation / tolerance / Cell ceparation |
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| Research Abstract |
Introduction : A number of experimental studies have shown the induction and maintenance of specific unresponsiveness or tolerance using donor antigens. However, most approaches require pretransplant strategies which are not feasible in clinical transplantation. In this study, we attempted to establish the simultaneous strategy with transplantation.
Objective : We evaluated the effect of donor lymphocyte subsets inoculation to prolong cardiac allograft survival.
Methods : BN rats were used as donors and LEW rats were as recipients of heart transplantation. Lymphocyte subsets were prepared from BN spleen cells by using magnetic beads (Dynabeads). The purity of fractionated splepocyte subsets were 90% (B cell), 90% (CD4 Tcell) and 65% (CD8 T cell). Experimental 1 ; We injected donor splenocytes or lymphocyte subsets (2x 10') simultaneously with heterotopic heart transplantation. FK5O6 (0.5mg/kg, intramuscular treatment) was administered on day -1,0, and 1. Group 1 (no treatment), Group 2 (FK506 alone), Group 3 (splenocytes with FK506), Group 4 (CD4), Group 5 (CD8) and Group 6 (B cells). Experimental 2 ; We injected donor B cells (5x10') simultaneously with transplantation. FK506 (1mg/kg) was administered on days 0-2. Group 7 (FK506 alone) and Group 8 (B cells with FK506).
Results : The graft survival time was as follows. Group 1 (n=5, 6.8*0.4 days), 2 (n=7, 13.7*2.7), 3 (n=7 15.7*5.3), 4 (n=7, 10.0*1.5), 5 (n=7, 10.4*1.6) and 6 (n=6, 19.5*4.4). Group 6 v.s.Group 2 (p=O.O14). Furthermore, Group 7 (n=3, 33.0*3.7) and Group 8 (n=4, 48.3*14.0).
Conclusion : B lymphocytes were more effective than T cells in prolonging donor graft survival. We speculate that B cells might act as antigen presenting cells and inactivate T cells. However, the effect was limited and insufficient. If more clinically applicapable and feasible strategies using B cells are established, we may induce donor specific tolerance.
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