2005 Fiscal Year Final Research Report Summary
Oral Tolerance Induction by Type V Collagen in Lung Transplantation
| Project/Area Number |
15591466
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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 |
Thoracic surgery
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| Research Institution | Chiba University |
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Principal Investigator |
SEKINE Yasuo Chiba University, Graduate School of Medicine, Instructor, 大学院・医学研究院, 助手 (70312957)
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| Co-Investigator(Kenkyū-buntansha) |
YASUFUKU Kazuhiro Chiba University, Hospital, Instructor, 医学部附属病院, 助手 (60372356)
YAMADA Yoshito Chiba University, Hospital, Fellow, 医学部附属病院, 医員 (80375691)
FUJISAWA Takehiko Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110328)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Lung Transplantation / Oral Tolerance / Type V Collagen / Allograft Rejection |
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| Research Abstract |
Objective : Lung allograft rejection involves an immune response to type V collagen [col(V)]. Oral tolerance induced by col(V) abrogates delayed type hypersensitivity (DTH) responses to donor antigens, and prevented acute and chronic lung allograft rejection. These data suggest that col(V)-induced tolerance might have stimulated regulatory T cells that suppress rejection responses. The purpose of the current study was to determine if col(V) oral tolerance induced regulatory T cells, and to determine the mechanism of immune suppression induced by these cells utilizing F344 lung allografts (RT1^<lv1> for orthotopic transplantation into WKY (RT1^1) rat recipients.
Materials and Methods : We utilized our recently described model of col(V)-induced oral tolerance to lung allografts in which feeding col(V) to WKY rats prior to transplantation induced tolerance to F344 lung allografts. CD4+ and CD8+ T cells were purified from spleens of different groups of WKY rats including tolerant rats and used for adoptive transfer studies. DTH responses and rejection pathology were assessed in different groups of adoptively transferred animals.
Results : Data showed that adoptive transfer of CD4+, but not CD8+, T cells from tolerant rats to untreated allograft recipients abrogated DTH responses to donor antigens, and prevented acute and chronic lung allograft rejection. MLR's revealed that CD4+ T cells from tolerant rats produced TGF-β constitutively and in response to alloantigen. Finally, anti- TGF-β antibodies recovered DTH responses suppressed by adoptive transfer of "tolerant" CD4+ T cells.
Conclusion : We conclude that col(V)-induced oral tolerance results in activity of regulatory CD4+ T cells that suppress alloreactivity by production of TGF-β.
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