| Project/Area Number |
14570406
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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 |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HOSONO Osamu The University of Tokyo, Institute of Medical Science, Reserch Assistant, 医科学研究所, 助手 (50190210)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | CD26 / ganglioside / T cells / immune response / Caveolin / dipeptidylpeptidase IV / Caveolin-1 / dipeptidyl peptidase IV |
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| Research Abstract |
CD26 and ganglioside GD3 are preferentially expressed on memory T cell migration and activation. Regulatory mechanism of T cell immune response mediated by CD26 and ganglioside GD3 was studied in this research.
1.Novel CD26 associated molecule: Novel CD26 binding protein was eluted from cell lysate of monocyte-derived cell line. THP-1, and was determined as caveolin-1. Scaffolding domain of caveolin-1 was required for binding to CD26. Caveolin-1 was expressed on the surface of monocytes after antigen stimulation and could enhance the expression of CD86 on monocytes through binding to soluble CD26.
2.Analysis of enhanced transendothelial migratory activity of CD26 and GD3 positive T cells: CD26 positive T cells could transmigrate after adhesion to the endothelial cells through LFA-1. In addition, GD3 positive T cells could spontaneously transmigrate through interaction between GD3 and some molecules on the surface of endothelial cells. In lymphocytes with enhanced expression of CD26 and GD3, Cas-L (Crk-associated substrate lymphcyte type) expression and phosphorylaton were augumented. These results indicated that Cas-L play a critical role in transendothelial migratory activity of CD26 and GD3 strongly positive T cells.
3.Regulation of T cell function by antibodies against CD26 and GD3: Cross-linking by anti-CD26antibody could increase CD26 molecule in the raft and induce tyrosine phosphorylation of c-Cbl, ZAP70, ERK1/2, and TCRζ. Binding of the soluble anti-CD26 antibody could inhibit T cell growth by inducing GI/S arrest, which is associatd with enhancement of p21^<Cipl> iexpression. Anti-GD3 antibody induced apoptosis of some GD3 positive cells. GD3 was co-localized wih lyn and caveolin-1, not with ganglioside GM1 in rafts recognized by cholera toxin B (CTB).
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