| Project/Area Number |
12470050
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
ONOE Kazunori Hokkaido Univ. Institute for Genetic Medicine., Prof., 遺伝子病制御研究所, 教授 (40002117)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGAWA Yoshiki Hokkaido Univ. Institute for Genetic Medicine, Inst., 遺伝子病制御研究所, 助手 (20322852)
IWABUCHI Kazuya Hokkaido Univ. Institute for Genetic Medicine, Asso. Prof., 遺伝子病制御研究所, 助教授 (20184898)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥15,700,000 (Direct Cost: ¥15,700,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥13,100,000 (Direct Cost: ¥13,100,000)
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| Keywords | NK-T cell / autoimmune / cytokine / Th1 and Th2 / CD8 molecule / syngenic MLR / 前駆細胞 / ZAP-70 / 胸腺器官培養 / 2Cトランスジェニックマウス |
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| Research Abstract |
1.Direct precursors of NK-T cells were identified in ZAP-70-/-mice and RAG-/-mice. These were NK1.1^+,TCR^-and exhibited a unique phenotype similar to NK cells. Upon stimulation with PMA +ionomycin, these precursors differentiated into NK-T cells in a neonatal thymic organ culture.
2.A normal population of NK-T cells were found in 2C transgenic mice with TCR specific for MHC class I. In the negative MHC background(H-2^d) the major population of NK-T cells were CD4,8 double negative, whereas in the positive background(H-2^b) the major NK-T cells were CD8 single positive. These NK-T cells produced a large amount of IFN-γ but not IL-4 upon stimulation with anti-CD3 mAb in vivo. No NK-T cells were generated in the neutral background(H-2^k). CD1 molecules appeared not to be involved in the selection of NK-T cells.
These findings demonstrate that a certain population of NK-T cells has been developed under the influence of MHC but not CD1 molecules.
3.Proliferation of NK-T cells was detected in syngeneic mixed lymphocyte response(SMLR) where purified dendritic cells were stimulators. The antigen system that NK-T cells recongnize in the SMLR is now under investigation.
4.Age-related decrease in the proportion of NK-T cells was found in New Zealand strains of mice, autoimmune prone a strains, but not in another autoimmune prone strain, 1pr mice. It appeared that these decreases were associated with the high complement sensitivity of NK-T cells.
5.Using aly/aly mice it shown that thymic medullary epithelial cells were indispensable to generation of NK-T cells.
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