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Establishment of producing immunologic tolerance by intrathymic antigen inoculation

Research Project

Project/Area Number 17580281
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionYamaguchi University

Principal Investigator

UNE Satoshi  Yamaguchi University, Agriculture, Associate Professor, 農学部, 助教授 (60294659)

Co-Investigator(Kenkyū-buntansha) TAURA Yasuho  Yamaguchi University, Agriculture, Professor, 農学部, 教授 (80163153)
NAKAICHI Munekazu  Yamaguchi University, Agriculture, Professor, 農学部, 教授 (60243630)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsimmunology / transplantation・regenerative medicine / immune tolerance / thymus / diabetes mellitus / 胸腺
Research Abstract

We have focused on the dog and pig immune responses toward the pig as the donor source. Furthermore, we try to examined the potentialities of the producing tolerance by intrathymic injection.
Unmodified canine serum caused approximate 100% PK15 cell. 5 carbohydrates (N-acetyl-β-D-Mannosamine, a -D-Galactose-1-phosphate, Arabinogalactan, Galactal(ICN) and N-acetyl-β-D-Glucosamine) were inhibited the cell damage against canine serum (47.4, 45.2, 34.8, 25.0, 23.1% respectively). And they were mixed, it was showed the protective effect (76.5%). The combine with PK15 cells and WGA lectin was obtained inhibition of PK15 cell damage. This study provides the evidence that (1) there are some carbohydrates on PK15 cells that may be the target against canine anti pig antibodies, (2) there may be useful role for inhibition to binding between carbohydrates as antigen and canine anti pig antibodies in order to prevent hyperacute rejection.
NIH minipigs were injected into either the thymus (Thymus grou … More p) or the spleen (Spleen group) with islets. In the Thymus group: 1) Anti-donor stimulation indices (SI) of mixed lymphocyte reactions (MLR) decreased, and remained low; 2) Peripheral blood lymphocytes (PBL) showed minimal cytotoxic activities in cell mediated lymphocytotoxicity (CML) assays; 3) Anti-donor cytotoxic T lymphocyte (CTL) activities in MLR-CML became undetectable; 4) Precursors of proliferating T lymphocytes (PTL-p) against donor LC decreased to an undetectable level; 5) Anti-donor cytotoxic antibodies were not detected; In contrast, in the Spleen group at 1 month: 1) Anti-donor SI of MLR increased; 2) Anti-donor cytotoxic activities increased in both CML and MLC-CML; 3) The PTL-p against donor LC increased; 4)Anti-donor antibodies were detectable starting from 1 week. These results demonstrated that intrathymic inoculation of islets induces unresponsiveness of PBL as well as suppression of systemic anti-donor cytotoxic antibody, and maintenances stable unresponsiveness directed against donor, but not third-party antigens. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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