| Project/Area Number |
10670121
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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 |
General medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SHIMIZU Akira Kyoto University, Center for Molecular Biology and Genetics, Professor, 遺伝子実験施設, 教授 (00162694)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Neonatal Thymectomy / Autoimmune Gastritis / Th1 / Th2 subsets / IL-4 / γ-Interferon / Transendothelial Migration / Endothelial Cells / CD4ィイD1+ィエD1 Killer Cells / Th2サブセット / ケモカイン / T細胞受容体遺伝子導入マウス |
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| Research Abstract |
A vast majority of CD4+ T cells infiltrating into gastric mucosa and in the gastric lymph node shows activated memory phenotype, CD45RBィイD1lowィエD1 L-selectinィイD1lowィエD1 CD44ィイD1highィエD1, in neonataly thymectomized BALB/c mice bearing autoimmune gastritis (AIG), indicating that these cells are actively involved in this disease. CD4ィイD1+ィエD1 T cells of gastric lymph node expressed both of mRNAs encoding IFN-γ and IL-4. However, those infiltrating into gastric mucosa expressed very low level of IL-4 mRNA, even though they strongly expressed IFN-γ mRNA. Among CD4ィイD1+ィエD1 T cells separated from AIG mice expressing detectable levels of either IFN-γ or IL-4 by intracellular staining, only less than one seventh expressed IL-4 and thus most of them expressed IFN-γ in gastric mucosa whereas roughly the half and one third expressed IL-4 in gastric lymph node and spleen, respectively. These findings indicate that the Th1 cells predominantly infiltrate into autoimmune lesions and Th2 cells are mainly resident in the regional lymph node. We further set up an in vitro model system of transendothelial migration using a murine endothelial cell line. F-2. and found that Th1 cells in CD4ィイD1+ィエD1 T cells separated from lymphoid tissues of AIG mice preferentially passed through the monolayer of endothelial cells while little portion of Th2 cells did so. Such different ability of transendothelial migration and localization might explain the dominance of Th1 cells destroying the tissue in focal lesion without inhibition by the Th2 cells, in spite of both of subsets simultaneously activated in AIG mice and the functions of each T cell subset seem to be mutually exclusive. Using Th1 and Th2 cells, taken from normal or TCR transgenic mice and induced in vitro, such differential transendothelial migration was reproduced. Therefore preferential transendothelial migration seems to be a general character of Th1 cells.
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