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1997 Fiscal Year Final Research Report Summary

Murine IL-4 Transgenic Heart Allograft Survival Prolonged With Downregulation of Th1 Cytokine mRNA in Grafts.

Research Project

Project/Area Number 08671798
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionUniversity of Tokyo

Principal Investigator

TOMITA Kyoichi  University of Tokyo Hospital, Dept.of Urology, Assistant Professor, 医学部・附属病院, 助手 (20272578)

Project Period (FY) 1996 – 1997
KeywordsIL4 / Th2 / Transplantation
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.

  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Takumi Takeuchi et al.: "Murine IL-4 Transgenic Heart Allograft Survival Prolonged With Downregulation of Th1 Cytokine mRNA in Grafts." Transplantation. 64. 152-157 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takumi Takeuchi et al.: "Murine IL-4 Transgenic Heart Allograft Survival Prolonged With Downregulation of Th1 Cytokine mRNA in Grafts." Transplantation. 64. 152-157 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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