| Project/Area Number |
15590282
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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 |
Pathological medical chemistry
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| Research Institution | TOIN HUMAN SCIENCE AND TECHNOLOGY CENTER, TOIN UNIVERSITY OF YOKOHAMA |
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Principal Investigator |
NISHIMURA Hiroyuki Toin University of Yokohama, Professor, 医用工学部, 教授 (60189313)
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| Co-Investigator(Kenkyū-buntansha) |
KODERA Yo Toin University of Yokohama, Associate Professor, 医用工学部, 助教授 (80205426)
HIROSE Sachiko Juntendo University Sch.Med., Associate Professor, 医学部, 助教授 (00127127)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | immune tolerance / autoimmune disease / SLE / systemic lupus erythematosus / NZB mice / disease susceptibility gene / genetic linkage study / Fc receptor / 全身性自己免疫疾患 / 遺伝支配 / C57BL / 6系マウス / 免疫グロブリン / ポリエチレングリコール / 連鎖解析 / 疾患感受性 / ゲノムマッピング / New Zealand系マウス / NZW系マウス |
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| Research Abstract |
The F1 hybrid of autoimmune hemolytic anemia-prone NZB and phenotypically normal NZW strains of mice has been studied as a murine model of systemic lupus erythematosus. Both NZB and F1 hybrid mice show age-dependent spontaneous activation of peripheral CD4^+ T cells as reflected by the elevated frequencies of CD4+ T cells positive for CD69 early activation marker. Both strains also show age-dependent abnormal decrease of the frequencies of CD62L+ naive CD4+ T cells and/or NTA260+ memory CD4^+ T cells in the spleen. We studied the multigenic control of these abnormal features of peripheral CD4^+ T cells in (NZB x NZW) F1 x NZW backcross mice by QTL mapping and by association rule analysis. The abnormally elevated frequencies of CD69^+CD4^+ T cells and decreased frequencies of CD62L^+ naive and/or NTA260^+ memory CD4^+ T cells were under the common genetic control, in which the interaction between MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell activation) on chromosome 12, plays a major role. The allelic effects of these loci likely predispose CD4^+ T cells to the loss of self-tolerance, and are responsible for the accelerated autoimmune phenotypes of (NZB x NZW) F1 hybrid m
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