PATHOGENIC ANTI-DNA AUTOANTIBODY-INDUCING T-HELPER CELL-LINES FROM PATIENTS WITH ACTIVE LUPUS NEPHRITIS - ISOLATION OF CD4-8- T-HELPER CELL-LINES THAT EXPRESS THE GAMMA-DELTA-T-CELL ANTIGEN RECEPTOR
PATHOGENIC ANTI-DNA AUTOANTIBODY-INDUCING T-HELPER CELL-LINES FROM PATIENTS WITH ACTIVE LUPUS NEPHRITIS - ISOLATION OF CD4-8- T-HELPER CELL-LINES THAT EXPRESS THE GAMMA-DELTA-T-CELL ANTIGEN RECEPTOR
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DOI：
10.1073/pnas.87.18.7020
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
DATTA, SK
中科院分区：
文献类型：
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作者：
RAJAGOPALAN, S;ZORDAN, T;DATTA, SK
引起系统性红斑狼疮自身免疫的抗原尚不清楚。尽管有这个障碍，我们表明，辅助性T细胞（Th）的功能相关的这种疾病可以在体外建立。我们从5例狼疮性肾炎患者体内活化的T细胞中获得了396个白细胞介素2依赖性T细胞系。只有59个（这些品系中的15%具有选择性地增强病原体抗DNA自身抗体的产生的能力，所述病原体抗DNA自身抗体是IgG类的、阳离子电荷的、对天然DNA特异的、并且在谱型中是克隆限制的。这些自身抗体诱导Th系中的49个是CD 4+并表达α。β的T细胞受体（TCR）。其他10例为CD 4 -8-（双阴性），3例表达α。β的TCR和表达γ的7个。δ的TCR。所有自身抗体诱导的Th细胞对自体B细胞呈递的内源性抗原都有应答。CD 4 + Th细胞系的自身反应性反应仅限于HLA II类抗原，而双阴性细胞则不限于HLA II类抗原。狼疮患者B细胞表达的HSP 60家族的内源性热休克或应激蛋白参与刺激γ细胞的自身反应性增殖。δ的Th细胞。这些研究证明了某些γ的新的辅助活性。δ的自发性自身免疫反应中的T细胞。
The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. Inspite of this obstacle, we show that T helper (Th) cells that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (.apprxeq. 15%) of these lines had the ability to selectively augmented the production of pathogenc anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the .alpha..beta. T-cell receptors (TCR). The other 10 were CD4-8- (double negative), 3 expressing the .alpha..beta. TCR and 7 expressing the .gamma..delta. TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients'' B cells were involved in stimulating an autoreactive proliferation of the .gamma..delta. Th cells. These studies demonstrate a novel helper activity of certain .gamma..delta. T cells in a spontaneous autoimmune response.