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

已知MRL小鼠的两个同源株：MRL/LPR小鼠具有LPR基因，MRL/+小鼠具有野生型基因。尽管存在不同的LPR基因，但由MRL/LPR骨髓细胞重组的MRL/+小鼠出现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CD4T细胞株(L/+T1)，并检测了L/+T1细胞的体内外特性。L/+T1细胞在体外表现出对自身I-E^K分子的增殖反应。结论1.B细胞对L/+T1细胞有较高的刺激活性(2)。L/+T1细胞在体外可以诱导I-E、K-B细胞的增殖和分化，并诱导包括自身抗体(抗单链DNA抗体和类风湿因子)在内的LGM的产生。3.注射L/+T1细胞给H-2^k小鼠(MRL/+和AKR)，而不注射给H-2^d小鼠，可诱导受体脾细胞在注射后1~2个月的自身反应性增强。注射还能增强…MRL/+小鼠产生较多的Ig G RF，AKR小鼠产生较少的Ig G和Ig M Rf。然而，注射L/+T1细胞不能增加自身抗体的产生，提示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L/+T1细胞共培养时，异常T细胞有向CD8+T细胞转化的趋势。但与对照相比，转化效果不明显。用L/+T1细胞免疫MRL/+小鼠，建立了杂交瘤细胞株(25T3，IgM，k)。25T3单抗是T细胞的特异性抗体，可与约90%的胸腺细胞发生反应。在脾T细胞中，约90%的CD8^+细胞对25T3反应抗原(25T_3-Ag)呈阳性反应，而CD_4~++T细胞因其表面表达的25T_3-Ag而分为两类：CD_4~++25T_3-Ag^+细胞相对对应于Th1细胞，而CD_4~++25T_3^+细胞相对对应于Th2细胞。经SDS-PAGE分析，25T3-Ag的分子量约为70 kDa。L/+T1细胞25T3-Ag阳性，25T3mAb可用于自身免疫性疾病和LPR-GVHD的分析。较少

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