Effector Th-1 cells with cytotoxic function in the intestinal lamina propria of patients with Crohn's disease

A large body of evidence points to a pivotal relationship between Th-1 cell s and mucosal inflammation in Crohn's disease (CD). The aim of the present study was to assess whether CD is associated with specific functional activ ity of lamina propria T lymphocytes (LPT), particularly purified CD4, such as cytotoxic activity and specific cytokine-secreted profile. The results s howed that CD4 LPT in patients displayed a chronically activated memory-lik e surface phenotype and, when compared to controls, had a significantly enh anced antibody-redirected cytotoxicity. Interestingly, the ratio of perfori n expression in CD4 LPT was higher compared to controls, and a redirected l ysis 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 w as detected, while IL-5 was undetectable. Our studies suggest that these pr eexisting in vivo activated CD4 LPT may play an important role in the infla mmatory process in CD, thus directly contributing to the intestinal lesions .