1997 Fiscal Year Final Research Report Summary
Murine IL-4 Transgenic Heart Allograft Survival Prolonged With Downregulation of Th1 Cytokine mRNA in Grafts.
| Project/Area Number |
08671798
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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 |
Urology
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| Research Institution | University of Tokyo |
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Principal Investigator |
TOMITA Kyoichi University of Tokyo Hospital, Dept.of Urology, Assistant Professor, 医学部・附属病院, 助手 (20272578)
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| Project Period (FY) |
1996 – 1997
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| Keywords | IL4 / Th2 / Transplantation |
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| Research Abstract |
(Background) Data supporting the differential activation of Th2 cells in transplantation acceptance/tolerance in rodents have been presented by several investigators. However, this may be simply the result of allograft acceptance/tolerance induction instead of a contribution to the maintenance of grafts. (Methods) Therefore, we established IL-4 transgenic mice underthe control of cardiac a-myosin heavy chain promotor and transplanted IL-4 expressing heart allografts into unmodified recipients to determine the actual contribution of the Th2 bias to allograft acceptance. (Results) Among 16 newborn B6 mice, three were positive for the IL-4 transgene. Serum IL-4 levels of transgenic versus control B6xC3H Fl were not statistically different. RT-PCR showed that the transgenic B6xC3H Fl expressed IL-4 mRNA in the heart and in the lung, whereas controls did not express IL-4 in any organ. IL-4 mRNA expression in the transgenic but not in the control heart was also confirmed by RNAse protection assay and fluorescence in situ hybridization. The survival of IL-4 transgenic B6xC3H heart grafts heterotopically placed in 03H recipients was prolonged compared with that of non-traisgenic grafts (19.0*9.1 vs 6.8*2.2 days, p=O.003). IFN-g mRNA expression in IL-4 transgenic heal grafts on the fifth post-transplant day assessed by Northern blotting was suppressed compared with that in control grafts. RT-PCR analysis showed that IL-2 mRNA was suppressed in IL-4 transgenic graft compared with that in control, while IL-4 mRNA was observed only in the IL-4 transgenic graft and IL-10 mRNA was detected at similar levels in both transgenic and control grafts. (Conclusions) A Th2 bias may contribute to allograft acceptance in part, by inducing the downregulation of Th1-cytokine mRNAs, but it may not be sufficient to induce indefinite graft survival.
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