| Project/Area Number |
17590676
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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 |
Gastroenterology
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
NAKAZAWA Stsushi Keio University, school of medicine, instructor, 医学部, 助手 (90255456)
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| Co-Investigator(Kenkyū-buntansha) |
HIBI Toshifumi Keio University, school of medicine, professor, 医学部, 教授 (50129623)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| 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)
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| Keywords | inflammatory bowel disease / epithelial cell / regulatory T cell / homeostasis / B7h / CD8 T cell / immunoregulatory therapy / Cbl-b / ホメオスタシス / 抑制性CD8^+T細胞 / Cb1-b |
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| Research Abstract |
1.Previous studies have suggested that intestinal epithelial cells (IECs) may function as antigen-presenting cells for T cells. Recently identified B7 family, B7h interacts with inducible costimulator (ICOS) on T cells and provides a stimulatory signal. To determine whether IECs express novel B7h and whether this molecule plays a role in IEC : T-cell interactions. B7h expression was assessed in isolated IECs. The functional role of B7h in the interaction between IECs and T cells was assessed in coculture experiments using purified anti-B7h mAbs and B7h fusion protein. IECs from patients with inflammatory bowel disease (IBD) but not healthy controls expressed B7h on their surface. Proliferation of IEC-stimulated T cells was inhibited by B7h fusion protein and anti-B7h mAb. These data suggest that the B7h-ICOS costimulatory pathway may be important in IEC : T-cell interactions..
2.CD45RBhi transfer colitis model were treated by colonic epithelial cells stimulated regulatory mucosal T lymphocytes at the time of transfer, and these murine model were ameliorated significantly. We will utilize this regulatory lymphocyte for the treatment with IBD patients.
3.Mucosal tolerance is believed to be partly mediated by regulatory T cells. We have analyzed lamina propria (LP) lymphocytes for the presence of such regulatory CD8^+ T cells in healthy controls as well as in patients with IBD. LP CD8^+ T cells derived from healthy controls possess regulatory activity. The LP CD8^+ T cells suppress Ig production by pokeweed mitogen-stimulated PBMCs. In contrast to CD8^+ T cells from normal LP, CD8^+ T cells isolated from LP of IBD patients, did not suppress Ig production. CD8^+ T cells with regulatory activity are present in the LP of healthy controls, but not in patients with IBD, suggesting that these cells might play an active role in mucosal tolerance.
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