In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice.
In vivo expression of perforin by CD8+ lymphocytes in autoimmune disease. Studies on spontaneous and adoptively transferred diabetes in nonobese diabetic mice.
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DOI：
10.4049/jimmunol.143.12.3994
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发表时间：
1989-12
影响因子：
4.4
通讯作者：
L. Young;L. Peterson;L. Wicker;P. Persechini;J. D. Young
中科院分区：
文献类型：
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作者：
L. Young;L. Peterson;L. Wicker;P. Persechini;J. D. Young
以前已经发现一种有效的细胞溶解性孔形成蛋白（穿孔素或细胞溶解素）与CTL和NK细胞的细胞质颗粒相关。由于所有先前关于穿孔素的研究都是用培养的CTL和NK细胞系进行的，因此尚不清楚穿孔素是否可能在体内引发的CTL介导的细胞毒性中起作用。在这项研究中，我们调查了存在穿孔素在胰腺从非肥胖糖尿病（NOD）小鼠，已被研究作为一种模型的自身免疫性，胰岛素依赖型（I型）糖尿病。尽管成年NOD小鼠自发地发生糖尿病，但通过过继转移从糖尿病供体获得的脾细胞，可以在年轻的、经辐射的NOD小鼠中诱导糖尿病。通过免疫组化分析，我们能够检测到穿孔素Ag在一个小的亚群的CD 8 +/Thy-1+/asialo GM 1-/CD 4-淋巴细胞在动物的胰岛进行自发性和过继性转移介导的胰岛炎。穿孔蛋白+/CD 8+淋巴细胞以小簇存在，并观察到显示大颗粒淋巴细胞的形态。这些观察结果首次显示了在经历自身免疫性疾病的动物组织中存在含穿孔素的CD 8+淋巴细胞。
A potent cytolytic pore-forming protein (perforin or cytolysin) has previously been found to be associated with the cytoplasmic granules of CTL and NK cells. Inasmuch as all previous studies on perforin have been conducted with cultured CTL and NK cell lines, it is not clear whether perforin may play a role in the cytotoxicity mediated by CTL that have been primed in vivo. In this study, we investigated the presence of perforin in pancreata from nonobese diabetic (NOD) mice, which have been studied as a model of autoimmune, insulin-dependent (type I) diabetes mellitus. Whereas adult NOD mice spontaneously develop diabetes, it is possible to induce diabetes in young, irradiated NOD mice by adoptive transfer of splenocytes obtained from diabetic donors. By means of immunohistochemical analysis, we were able to detect perforin Ag in a small subpopulation of CD8+/Thy-1+/asialo GM1-/CD4- lymphocytes in the pancreatic islets of animals undergoing both spontaneous and adoptive transfer-mediated insulitis. Perforin+/CD8+ lymphocytes were found in small clusters and were observed to display the morphology of large granular lymphocytes. These observations show for the first time the presence of perforin-containing CD8+ lymphocytes in tissues of animals undergoing autoimmune disease.