Mechanism for MHC class II E region-linked autoimmune suppression.

MHC II 类 E 区相关自身免疫抑制的机制。

• 批准号: 12670309
• 负责人: HIROSE Sachiko
• 金额: $ 2.11万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670309/
• 关键词: systemic lupus erythematosus; MHC class II; I-A molecule; I-E molecule; H-2 recombination; H-2-congenic mouse; suppressor T cells; MHC class II; H-2 recombination; H-2-congeuicマウス; ヘテロ接合性

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.

(NZB x NZW) F1 小鼠自发地患上类似于人类系统性红斑狼疮的自身免疫性疾病。疾病的发生受到主要组织相容性复合体（MHG）的H-2^<d/z>杂合性、NZB菌株的H-2^<d>和NZW菌株的H-2^<Z>的限制。对自身反应性 T 细胞克隆的研究表明，Aα^<d> Aβ^<z> 分子可能是加速疾病的候选分子。在本研究中，我们建立了携带H-2^<g2>单倍型的H-2同源NZB.GD和NZW.GD菌株，显示H-2^d和H-2^b单倍型之间的H-2内重组，这是发生在Ea亚区左侧的交换的结果。由于 Ea^b 是无效等位基因，因此这些同源菌株不表达 E 分子。 (NZB x NZW.H-2^d)F1、(NZB x NZW.GD)F1和(NZB.GD x NZW.GD)F1小鼠之间疾病严重程度的比较显示疾病严重程度由Ea连接的亚区控制并且Ea^d抑制疾病。此外，与未治疗的(NZB x NZW.GD)F1小鼠相比，用来自(NZB x NZW.H-2^<d>)F1小鼠的CD^8+T细胞转移的(NZB x NZW.GD)F1小鼠中的疾病严重程度被显着抑制。为了确定用于疾病抑制的精确亚区，我们一直在建立新的 H-2 重组同源菌株，其在 Ea 亚区右侧的 H-2^<d> 和 H-2^<b> 单倍型之间进行 H-2 内重组。 CD8^+ T 细胞抑制疾病的机制正在研究中。

项目成果

Hirose,S. et al.: "Genetic aspects of inherent B-cell abnormalities associated with SLE and B-cell' malignancy : Lessons from New Zealand mouse models."Int Rev.Immunol.. 19. 389-421 (2000)

广濑，S.

Hirose, S.et al.: "Genetic aspects of inherent B-cell abnormalities associated with SLE and B-cell malignancy : Lessons from New Zealand mouse models."Int Rev. Immunol.. 19. 389-421 (2000)

Hirose, S.等人：“与 SLE 和 B 细胞恶性肿瘤相关的固有 B 细胞异常的遗传方面：来自新西兰小鼠模型的教训。”Int Rev.Immunol.. 19. 389-421 (2000)

Shirai,T.& Hirose,S.: "Genetics of SLE ; A sine qua non for identification."Int Rev.Immunol.. 19. 289-295 (2000)

白井，T.

Hamano,Y.& Hirose,S.: "Microsatellite method.In Laboratory Techniques in Renal Cell and Molecular Biology."KARGER. (209)(156-161) (2000)

滨野，Y.

Hirose, S., et al: "Genetic basis of systemic lupus erythematosus"Drug of Today, Prous Science, Barcelona, Spain. (in press). (2002)

Hirose, S. 等人：“系统性红斑狼疮的遗传基础”《今日药物》，Prous Science，西班牙巴塞罗那。