2004 Fiscal Year Final Research Report Summary
Indefinite survival of fully mismatched cardiac graft by intratracheal delivery of alloantigen
| Project/Area Number |
15591363
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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 | Teikyo University |
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Principal Investigator |
NIIMI Masanori Teikyo University, School of medicine, Associate professor, 医学部, 助教授 (80198415)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Yoshifumi Teikyo University, School of medicine, Assistant professor, 医学部, 講師 (20222870)
HATANO Minoru Teikyo University, School of medicine, Lecturor, 医学部, 助手 (40365961)
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| Project Period (FY) |
2003 – 2004
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| Keywords | mice / cardiac grafts / donor antigen / oral tolerance / intratracheal delivery / regulatory cells / tolerance |
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| Research Abstract |
Background. The mechanism of hyporesponsiveness induced by intratracheal (IT) delivery of alloantigen was examined and its effect on cardiac graft survival was assessed in studies in mice.
Methods. In CBA (H2k) mice, donor splenocytes were given by IT delivery 7 days before transplantation of a C57BL/10 (H2b) heart. To determine whether regulatory cells were involved in hyporesponsiveness, splenocytes fro mice given IT delivery of alloantigen and antibodies for B7-1, B7-2, or CTLA4 were adoptively transferred to naive secondary recipients 7 days after delivery; those recipients underwent heart transplantation the same day. Effects on cell proliferation and cytokine production of splenocytes from mice given IT delivery of alloantigen were examined in mixed leukocyte cultures (MLC).
Results. Cardiac graft survival was significantly prolonged in mice given IT delivery of alloantigen (median survival time [MST], 81 days); those given syngeneic splenocytes rejected grafts acutely (MST, 7 days;P <0.05). Adoptive transfer of splenocytes also significantly prolonged survival of cardiac grafts in secondary recipients (MST, 62 days). When B7-1, B7-2, or CTLA4 antibody was combined with IT delivery of alloantigen in the first recipient, all grafts were rejected within 14 days in second recipients after adoptive transfer. In mixed leukocyte cultures, splenocytes from these mice did not respond to alloantigen and production of interleukin-4 and interleukin-10 was increased.
Conclusions. Donor splenocytes delivered IT induced hyporesponsiveness and regulatory cells in our animal model, and such induction was dependent on B7-1, B7-2, and CTLA4 signals.
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