Auto-MHC class II-reactive T cell line obtained from MRL mice

从 MRL 小鼠获得的自身 MHC II 类反应性 T 细胞系

• 批准号: 02670162
• 负责人: NAGATA Norikazu
• 金额: $ 1.47万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670162/
• 关键词: MRL; + mice; lpr mice; lpr-GVHD; Autoreactivity; MHC class II antigen; T cell clone; Autoantibody; Monoclonal antibody; lpr; GVHD; 自己MHC反応性; T細胞クロ-ン; モノクロ-ナル抗体; lprーGVHD; Autoreactive T cells; Autoanttdody

Two congenic strains of MRL mice are knwon; MRL/lpr mice possess lpr gene and MRL/+ mice posses wild type gene. Although they are different at the presence of lpr gene, lethally irradiated MRL/+ mice reconstituted with MRL/lpr bone marrow cells develop severe graft-versus-host disease (GVHD)-like syndrome which is known as lpr-GVHD (1). We have established a CD4^+ T cell line (l/+T1) and examined characteristics of l/+T1 cells in vitro and in vivo.1. L/+ T1 cells show prliferative response restricted to self-I-E^k molecule in vitro. B cells show relatively high stimulation activity to l/+T1 cells (2).2. L/+T1 cells can induce proliferation and differentiation of I-E^k B cells, and induce lgM production including autoantibodies (anti-ssDNA antibodies and rheumatoid factors (RF) in vitro (2). 3. Injection of l/+T1 cells to H-2^k mice (MRL/+ and AKR), but not to H-2^d mice, induces enhanced autoreactivity of recipient spleen cells 1 to 2 months after injection. The injection also enhances … More IgG RF prosuction in MRL/+ mice, and slightly IgG and IgM RF production in AKR mice. However, anti-ssDNA antibody production can not be augmented by the injection of l/+ T1 cells, suggesting that autoantibody production is dependent on the presence of antigen (3).4. When MRL/lpr abnormal T cells were co-cultured with l/+ T1 cells,abnormal T cells showed a tendency to convert to CD8^+ T cells. However, the conversion was not so marked comparing with control cultures.5. A hybridoma (25T3, IgM, k) was established from MRL/+ mice immunized with l/+T1 cells. 25T3 monoclonal antibody (mAb) is specific for T cells and reacts with approximately 90% thymocytes. In splenic T cells, approximately 90% CD8^+ cells are positive for 25T3-reactive antigen (25T3-Ag), and CD4^+ T cells are divided to two popualtions by their surface expression of 25T3-Ag; CD4^+25T3-Ag^+ cells relatively correspond to Thl cells and CD4^+25T3^- cel'ls to Th2 cells. 25T3-Ag is approximately 70 kDa by SDS-PAGE. L/+ T1 cells are positive for 25T3-Ag, 25T3 mAb may be useful to analyze autoimmune disease and lpr-GVHD (4). Less

已知MRL小鼠有两个同源品系，MRL/lpr小鼠具有lpr基因，MRL/+小鼠具有野生型基因。尽管它们在lpr基因存在时是不同的，但用MRL/lpr骨髓细胞重建的致死性辐照MRL/+小鼠发生了严重的移植物抗宿主病（GVHD）样综合征，称为lpr-GVHD（1）。我们建立了一个CD 4 ^+ T细胞系（1/+T1），并在体外和体内检测了1/+T1细胞的特性。L/+ T1细胞在体外表现出仅限于自身I-Ek分子的增殖反应。B细胞对1/+T1细胞显示出相对高的刺激活性（2）。L/+T1细胞可以诱导I-E^k B细胞的增殖和分化，并在体外诱导IgM产生，包括自身抗体（抗ssDNA抗体和类风湿因子（RF））（2）。3.将1/+T1细胞注射至H-2k小鼠（MRL/+和AKR），但不注射至H-2d小鼠，在注射后1至2个月诱导受体脾细胞的增强的自身反应性。注射也增强了 ...更多信息 MRL/+小鼠中IgG RF前抽吸，AKR小鼠中轻微IgG和IgM RF产生。然而，抗ssDNA抗体的产生不能通过注射1/+ T1细胞来增强，这表明自身抗体的产生依赖于抗原的存在（3）。当MRL/lpr异常T细胞与1/+ T1细胞共培养时，异常T细胞显示出向CD 8 ^+ T细胞转化的趋势。但转化率与对照组相比并不显著.用1/+T1细胞免疫MRL/+小鼠，建立杂交瘤细胞株（25 T3，IgM，k）。25 T3单克隆抗体（mAb）对T细胞具有特异性，与约90%的胸腺细胞反应。在脾T细胞中，约90%的CD 8 ^+细胞对25 T3-反应性抗原（25 T3-Ag）呈阳性，而CD 4 ^+ T细胞因其表面表达25 T3-Ag而分为两个群体：CD 4 ^+25 T3-Ag^+细胞相对对应于Th 1细胞，CD 4 ^+25 T3 ^-细胞相对对应于Th 2细胞。25 T3-Ag经SDS-PAGE分析约为70 kDa。L/+ T1细胞对25 T3-Ag呈阳性，25 T3 mAb可能有助于分析自身免疫性疾病和lpr-GVHD（4）。少

项目成果

T.Nakagawa,N.Nagata,N.Hosaka,M.Inaba,and s.Ikehara: "Analyses of acute graft-versus-host like reaction in[MRL/lpr→MRL/+]chimeric mice using MRL/lpr-Thy-1.1 congenic mice." Cell.Immunol.137. 189-199 (1991)

T.Nakakawa、N.Nagata、N.Hosaka、M.Inaba 和 s.Ikehara：“使用 MRL/lpr-Thy 分析 [MRL/lpr→MRL/+] 嵌合小鼠中的急性移植物抗宿主样反应-1.1 同类小鼠。”Cell.Immunol.137. 189-199 (1991)

長田 憲和,池原 進: "免疫毒性と自己免疫" 免疫薬理. 10. (1992)

Norikazu Nagata、Susumu Ikehara：“免疫毒性和自身免疫”免疫药理学 10。（1992）

N. Nagata, S. Taketani, Y. Adachi, N. Hosaka, S. Miyashima, R. Tokunaga, and S. Ikehara: "A monoclonal antibody reactive with a glycophosphatidylinositol-anchored molecule on T cells defines CD4^+ T cell subsets." Eur. J. Immunol.(1993)

N. Nagata、S. Taketani、Y. Adachi、N. Hosaka、S. Miyashima、R. Tokunaga 和 S. Ikehara：“与 T 细胞上糖磷脂酰肌醇锚定分子发生反应的单克隆抗体定义了 CD4+ T 细胞亚群。

N.Nagata et al.: "AutoーMHC class IIーreactive T cell line obtained form MRL/+ mice suffering from “lprーGVHD"I.Characterization of surface phenotypes" Immunobiology.

N.Nagata 等人：“从患有“lpr-GVHD”的 MRL/+ 小鼠中获得的 Auto-MHC II 类反应性 T 细胞系。I.表面表型的表征”免疫生物学。

N.Nagata,R.Yasumizu,Y.Ohnishi,T.Nakagawa,M.Inaba,and S.Ikehara: "Auto-MHC Class II-reactive T cell reactive T cell line obtained from MRL/+ mice suffering from “lpr-GVHD".I.Characterization of surface phenotypes,specificities and functions in vitro." Immu

N. Nagata、R. Yasumizu、Y. Ohnishi、T. Nakakawa、M. Inaba 和 S. Ikehara：“自 MHC II 类反应性 T 细胞反应性 T 细胞系从患有“lpr- GVHD“.I.体外表面表型、特异性和功能的表征。”