2001 Fiscal Year Final Research Report Summary
Mechanism for MHC class II E region-linked autoimmune suppression.
| Project/Area Number |
12670309
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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 |
Immunology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
HIROSE Sachiko Juntendo Univ., Dept. Pathol., Associate Proffessor, 医学部, 助教授 (00127127)
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| Co-Investigator(Kenkyū-buntansha) |
ZHANG Danqing Juntendo Univ., Dept. Pathol., Instructor, 医学部, 助手 (40296877)
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| Project Period (FY) |
2000 – 2001
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| Keywords | systemic lupus erythematosus / MHC class II / I-A molecule / I-E molecule / H-2 recombination / H-2-congenic mouse / suppressor T cells |
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| Research Abstract |
The (NZB x NZW) F1 mice spontaneously develop autoimmune disease resembling human systemic lupus erythematosus. The occurrence of disease is restricted by H-2^<d/z> heterozygosity of the major histocompatibility complex (MHG), H-2^<d> from NZB and H-2^<Z> of NZW strains. Studies on autoreactive T cell clones suggest that Aα^<d> Aβ^<z> molecules may be candidate for disease acceleration. In the present studies, we established H-2-congenic NZB.GD and NZW.GD strains carrying H-2^<g2> haplotype, showing the intra-H-2 recombination between H-2^d and H-2^b haplotype, as a result of crossing-over which occurred to the left of the Ea subregion. Because Ea^b is a null allele, these congenic strains do not express E molecules. Comparison of disease severity among (NZB x NZW.H-2^d) Fl, (NZB x NZW.GD) F1 and (NZB.GD x NZW.GD) Fl mice showed that disease severity is controlled by Ea-linked subregion and that Ea^d suppress the disease. Furthermore, the disease severity in (NZB x NZW. GD) F1 mice transferred with CD^<8+> T cells from (NZB x NZW.H-2^<d>) F1 mice was markedly suppressed, as compared with non-treated (NZB x NZW.GD) F1 mice. To identify exact subregion for disease suppression, we have been establishing new H-2 recombinant-congenic strains carrying intra-H-2 recombination between H-2^<d> and H-2^<b> haplotype to the right of Ea subregion. The mechanism for disease suppression by CD8^+ T cells is under investigation.
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Research Products
(16 results)
