2000 Fiscal Year Final Research Report Summary
Oral tolerance to allogeneic cardiac grafts
| Project/Area Number |
11671185
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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, Assist Prof, 医学部, 講師 (80198415)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Oral injection / anti-CD4 MAb / Cardiac grafts / Mice / Indirect pathway / MHC antigen / Mucosa / Oral tolerance |
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| Research Abstract |
BACKGROUND : We examined whether oral administration of alloantigen could induce the prolonged survival of cardiac allografts. METHODS : Hearts from CBK (H2k+Kb) transgenic or (C57BL/10xCBA) F1 (H2bxH2k) mice were transplanted into CBA (H2k) recipients pretreated orally with 1 x 10 (7) donor splenocytes in the presence or absence of a nondepleting anti-CD4 (YTS 177, 200 microg/dose). RESULTS : Modest prolongation of CBK cardiac grafts was induced in CBA mice fed with multiple doses of CBK splenocytes (MST 42 days compared with controls fed with syngeneic CBA splenocytes, 12 days). When the CD4 monoclonal antibody, YTS177, was administered for 2 days before the first oral delivery of CBK splenocytes, all mice accepted their grafts indefinitely (MST>1OO days versus mice treated with anti-CD4 alone, 11.5 days). To determine if feeding multiple doses of alloantigen was essential, CBA mice were given CBK splenocytes orally on a single occasion in combination with the anti-CD4. The majority of the grafts survived indefinitely (MST>100 days). This oral treatment regimen also induced indefinite prolongation of (C57BL/10xCBA) F1 cardiac grafts.
CONCLUSION : The induction of unresponsiveness by oral administration of alloantigen can be augmented by a nondepleting anti-CD4, YTS177, when given before the first oral delivery of allogeneic cells.
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Research Products
(10 results)
