T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis.
T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis.
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DOI：
10.1084/jem.180.6.2239
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发表时间：
1994-12-01
期刊：
影响因子：
--
通讯作者：
Kelly CJ
中科院分区：
文献类型：
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作者：
Weiss RA;Madaio MP;Tomaszewski JE;Kelly CJ
T细胞对诱导性热休克蛋白（HSPs）的免疫优势区有反应，已在几种实验性自身免疫性疾病的慢性炎性病变中发现。由于已知热休克蛋白是由与慢性间质性肾炎相关的许多肾小管上皮细胞毒素诱导的，我们在进行性炎性间质性肾炎模型中研究了热休克蛋白表达和T细胞对HSP70的反应性的相关性。慢性给药氯化镉（CdCl2）诱导SJL/J小鼠肾小管细胞在间质单核细胞浸润前4-5周表达HSP70。CdCl2在培养的SJL/J小鼠小管上皮细胞中也能诱导HSP70的表达。CD4+、tcr - α / β + T细胞系对热应激或cdcl2处理的肾小管细胞具有细胞毒性。当免疫反应性HSP70在肾脏中可检测到，但在间质单核细胞浸润发展之前，这种HSP70反应性T细胞过继转移到cdcl2处理的小鼠后介导炎症性间质性肾炎。从经CdCl2处理13周的小鼠肾病肾中分离出的T细胞也对热休克或镉处理的小管细胞具有细胞毒性。这些肾源性T细胞在被动转移后可诱导间质性肾炎，表明其致病意义。我们的研究强烈支持热休克蛋白反应性T细胞在cdcl2诱导的间质性肾炎中的作用，并表明通过大量“非免疫”事件在肾脏中诱导热休克蛋白可能启动或促进热休克蛋白反应性淋巴细胞的炎症损伤。
T cells reactive against immunodominant regions of inducible heat shock proteins (HSPs) have been identified in the chronic inflammatory lesions of several experimental autoimmune diseases. Since HSPs are known to be induced by a number of renal tubular epithelial cell toxins associated with chronic interstitial nephritis, we investigated the relevance of HSP expression and T cell reactivity to HSP70 in a model of progressive inflammatory interstitial nephritis. Chronic administration of cadmium chloride (CdCl2) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdCl2 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-alpha/beta+ T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdCl2-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdCl2-treated mice at a time when immunoreactive HSP70 is detectable in the kidneys, but before the development of interstitial mononuclear cell infiltrates. T cells isolated from the nephritic kidneys of mice treated with CdCl2 for 13 wk are also cytotoxic to heat shocked or cadmium-treated tubular cells. These kidney-derived T cells additionally induced interstitial nephritis after passive transfer, indicating their pathogenic significance. Our studies strongly support a role for HSP-reactive T cells in CdCl2-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "non-immune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.