CD4+ T cells play an important role in acute experimental pancreatitis in mice
CD4+ T cells play an important role in acute experimental pancreatitis in mice
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DOI：
10.1016/s0016-5085(00)70265-4
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发表时间：
2000-03-01
期刊：
影响因子：
29.4
通讯作者：
Devière, J
中科院分区：
文献类型：
--
作者：
Demols, A;Le Moine, O;Devière, J
背景与目的：关于T淋巴细胞在实验性急性胰腺炎中的潜在作用的数据很少。本研究的目的是表征它们在急性胰腺炎的炎症级联反应中的作用。方法：在裸鼠和体内CD4（+）或CD8(+) T细胞缺失小鼠中反复注射蓝蛋白诱导急性胰腺炎。使用抗cd40配体或抗b7 -1和-B7-2单克隆阻断抗体评估T淋巴细胞共刺激通路的作用。利用Fas配体靶向突变（全身性淋巴细胞增生性疾病）小鼠，探讨Fas-Fas配体的作用。通过血清水解酶水平和组织学评估急性胰腺炎的严重程度，通过逆转录聚合酶链反应检测胰腺内白细胞介素12、干扰素γ、Fas配体和CD40配体信使RNA。免疫组化法检测胰腺内T淋巴细胞。结果：在对照组小鼠中，胰腺中存在T细胞，并在急性胰腺炎期间被募集，其中大部分是CD4(+) T细胞。在裸鼠中，组织学病变和血清水解酶水平显著降低。t淋巴细胞转染裸鼠可部分恢复急性胰腺炎的严重程度和胰脏内干扰素γ、白细胞介素12和Fas配体基因转录。在体内CD4(+)（而不是CD8(+)） t细胞消耗和Fas配体靶向突变小鼠中，胰腺炎的严重程度也会降低。阻断CD40-CD40配体或B7-CD28共刺激通路对胰腺炎的严重程度没有影响。结论：T淋巴细胞，特别是CD4(+) T细胞在小鼠急性实验性胰腺炎的组织损伤中起关键作用。
Background & Aims: Few data are available on the potential role of T lymphocytes in experimental acute pancreatitis. The aim of this study was to characterize their role in the inflammatory cascade of acute pancreatitis. Methods: To type this issue, acute pancreatitis was induced by repeated injections of cerulein in nude mice and in vivo CD4(+) or CD8(+) T cell-depleted mice. The role of T lymphocyte-costimulatory pathways was evaluated using anti-CD40 ligand or anti-B7-1 and -B7-2 monoclonal blocking antibodies. The role of Fas-Fas ligand was explored using Fas ligand-targeted mutant (generalized lymphoproliferative disease) mice. Severity of acute pancreatitis was assessed by serum hydrolase levels and histology, Intrapancreatic interleukin 12, interferon gamma, Fas ligand, and CD40 ligand messenger RNA were detected by reverse-transcription polymerase chain reaction. Intrapancreatic T lymphocytes were identified by immunohistochemistry. Results: In control mice, T cells, most of them CD4(+) T cells, are present in the pancreas and are recruited during acute pancreatitis. In nude mice, histological lesions and serum hydrolase levels are significantly decreased. T-lymphocyte transfer into nude mice partially restores the severity of acute pancreatitis and intrapancreatic interferon gamma, interleukin 12, and Fas ligand gene transcription. The severity of pancreatitis is also reduced by in vivo CD4(+) (but not CD8(+)) T-cell depletion and in Fas ligand-targeted mutant mice. Blocking CD40-CD40 ligand or B7-CD28 costimulatory pathways has no effect on the severity of pancreatitis. Conclusions: T lymphocytes, particularly CD4(+) T cells, play a pivotal role in the development of tissue injury during acute experimental pancreatitis in mice.