Mariani P, Bachetoni A, D'Alessandro M, Lomanto D, Mazzocchi P, Speranza V
Istituto 2a Clinica Chirurgica, Università La Sapienza, Rome, Italy.
Dig Dis Sci. 2000 Oct;45(10):2029-35. doi: 10.1023/a:1005516730754.
A large body of evidence points to a pivotal relationship between Th-1 cells and mucosal inflammation in Crohn's disease (CD). The aim of the present study was to assess whether CD is associated with specific functional activity of lamina propria T lymphocytes (LPT), particularly purified CD4, such as cytotoxic activity and specific cytokine-secreted profile. The results showed that CD4 LPT in patients displayed a chronically activated memory-like surface phenotype and, when compared to controls, had a significantly enhanced antibody-redirected cytotoxicity. Interestingly, the ratio of perforin expression in CD4 LPT was higher compared to controls, and a redirected lysis of human RBC mediated by a CD4 subset of intestinal lamina propria was evident, suggesting a cytolytic pore-forming mechanism. Moreover, a unique Th-1 cytokine profile pattern in the CD4 cells from CD was defined. These effector cells produced 12 times more IFN-gamma, two times more TNF-alpha, and three times less IL-4 than controls. In contrast, no increase in IL-2 was detected, while IL-5 was undetectable. Our studies suggest that these preexisting in vivo activated CD4 LPT may play an important role in the inflammatory process in CD, thus directly contributing to the intestinal lesions.
大量证据表明，Th-1细胞与克罗恩病（CD）的黏膜炎症之间存在关键关系。本研究的目的是评估CD是否与固有层T淋巴细胞（LPT）的特定功能活性相关，特别是纯化的CD4，如细胞毒性活性和特定的细胞因子分泌谱。结果显示，患者的CD4 LPT表现出慢性激活的记忆样表面表型，与对照组相比，其抗体重定向细胞毒性显著增强。有趣的是，与对照组相比，CD4 LPT中穿孔素的表达比例更高，并且由肠道固有层的CD4亚群介导的人红细胞重定向裂解明显，提示存在溶细胞性成孔机制。此外，还确定了CD患者CD4细胞中独特的Th-1细胞因子谱模式。这些效应细胞产生的IFN-γ比对照组多12倍，TNF-α多2倍，IL-4少3倍。相比之下，未检测到IL-2增加，而IL-5无法检测到。我们的研究表明，这些体内预先存在的活化CD4 LPT可能在CD的炎症过程中起重要作用，从而直接导致肠道病变。
