T-CELL RECEPTOR V-BETA GENES EXPRESSED BY IGG ANTI-DNA AUTOANTIBODY-INDUCING T-CELLS IN LUPUS NEPHRITIS - FORBIDDEN RECEPTORS AND DOUBLE-NEGATIVE T-CELLS
T-CELL RECEPTOR V-BETA GENES EXPRESSED BY IGG ANTI-DNA AUTOANTIBODY-INDUCING T-CELLS IN LUPUS NEPHRITIS - FORBIDDEN RECEPTORS AND DOUBLE-NEGATIVE T-CELLS
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DOI：
10.1002/eji.1830200705
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发表时间：
1990-07-01
影响因子：
5.4
通讯作者：
DATTA, SK
中科院分区：
文献类型：
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作者：
ADAMS, S;ZORDAN, T;DATTA, SK
在苏联时代。在狼疮性肾炎的NZB)F1 （SNF1）模型中，某些表型为CD4+或CD4- cd8 -（双阴性；DN）的T辅助（Th）细胞诱导了致病性IgG抗dna自身抗体的变化。从8只患有狼疮性肾炎的SNF1小鼠的脾脏中，获得149株T细胞系，其中只有25株（.apprxeq.）。17%)能够增加致病性抗dna自身抗体的产生。在此，我们分析了T细胞受体（TcR） v . β。16种致病自身抗体诱导的Th细胞系使用的基因。其中12株为CD4+， 5株中表达v . β（8.2或8.3）。V.beta。8基因家族是由NZB亲本贡献给SNF1小鼠的，因为它在SWR亲本株中不存在。另外三条CD4+ Th细胞系表达v . β。另一个是v。2株+株和1株自身抗体诱导能力较差的株表达v . β .1。来自SNF1小鼠的四种自身抗体诱导的Th系具有DN表型，这些系也具有自身反应性，对同基因脾细胞产生增殖反应。在这些DN - Th系中，有2株表达v - β。1例表达v . β .8.1 TcR。这两种都是针对SNF1小鼠表达的Mls-1a （Mlsa）自身抗原的禁用TcR，这些自身反应性T细胞应该在胸腺发生过程中被删除。因此，非lpr SNF1小鼠的DN Th细胞不同于DN细胞或MRL-lpr，后者缺乏辅助活性，不表达禁止的TcR。19只SNF1肾病动物中，有6只的脾脏也出现以DN为主的禁用自身反应性TcR+细胞的扩增。其中两只动物表达了高水平的v.a 6（anti-Mlsa）和v.a 11（抗i- e） TcR+细胞，另外三个有高水平的v - β。有11个以上的细胞，一只动物有扩大的v . β群体。17a+（抗i- e）细胞。在SNF1胸腺中，I-E反应性TcR也应该被消除，因为它们表达由NZB亲本贡献的I-E分子。SNF1的SWR亲本为I-E-；此外，它们缺乏v - beta。11基因，但它们表达v。外周T细胞中的17a。而NZB型父母是I-E+型，他们缺乏功能性的v - β。17a基因，他们删除了成熟的v。11+ T细胞。因此，从NZB和SWR亲本遗传的MHC II类和TcR基因的组合以及胸腺缺失/选择过程的异常可能在SNF1小鼠中产生自身抗体诱导的Th细胞。
In the (SWR .times. NZB)F1 (SNF1) model of lupus nephritis, pathogenic variety of IgG anti-DNA autoantibodies are induced by certain T helper (Th) cells that are either CD4+ or CD4-CD8- (double negative; DN) in phenotype. From the spleens of eight SNF1 mice with lupus nephritis, 149 T cell lines were derived and out of these only 25 lines (.apprxeq. 17%) were capable of augmenting the production of pathogenic anti-DNA autoantibodies. Herein, we analyzed the T cell receptor (TcR) V.beta. genes used by 16 such pathogenic autoantibody-inducing Th cell lines. Twelve of the Th lines were CD4+ and among these five lines expressed V.beta.8 (8.2 or 8.3). The V.beta.8 gene family is contributed by the NZB parent to the SNF1 mice, since it is absent in the SWR parental strain. Three other CD4+ Th lines expressed V.beta.4, another was V.beta.2+ and one line with poor autoantibody-inducing capability expressed V.beta.1. Four autoantibody-inducing Th lines from the SNF1 mice had a DN phenotype and these lines were also autoreactive, proliferating in response to syngeneic spleen cells. Among these DN Th lines, two expressed V.beta.6 and one expressed V.beta.8.1 TcR. Both of these are forbidden TcR directed against Mls-1a (Mlsa) autoantigens expressed by the SNF1 mice and such autoreactive T cells should have been deleted during thymic ontogeny. Thus, the DN Th cells of non-lpr SNF1 mice are different from the DN cells or MRL-lpr which lack helper activity and do not express forbidden TcR. The spleens of 6 out of 19 nephritic SNF1 animals tested also showed an expansion of forbidden autoreactive TcR+ cells that were mainly DN. Two of these animals expressed high levels of V.beta.6 (anti-Mlsa) and V.beta.11 (anti-I-E) TcR+ cells, three others had high levels of V.beta.11+ cells alone and one animal had an expanded population of V.beta.17a+ (anti-I-E) cells. The I-E-reactive TcR again should have been eliminated in the SNF1 thymus, since they express I-E molecules contributed by the NZB parent. The SWR parents of SNF1, are I-E-; moreover, they lack the V.beta.11 gene but they express V.beta.17a in peripheral T cells. Whereas the NZB parents are I-E+, they lack a functional V.beta.17a gene and they delete mature V.beta.11+ T cells. Thus, a combination of MHC class II and TcR genes inherited from the NZB and SWR parents and abnormalities in thymic deletion/selection processes may generate the autoantibody-inducing Th cells in the SNF1 mice.