Dilitiazem reduces nitric oxide production by human immune cells.
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Biomedical subjects
Publications and source records attributed to A Bachetoni.
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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.
The association between acute rejection, acute tubular necrosis, good function and relative infiltration of CD56 subsets of both CD8+ and CD4+ T cells was examined on 67 samples of graft infiltrating cells (GIC) and corresponding peripheral blood lymphocytes (PBL) obtained from renal allograft recipients. Quantification of cell subset profiles was determined by two-color flow cytometry. While a high proportion of CD4+CD56+ GIC was detected when both renal dysfunction and graft cytopathology (acute tubular necrosis or acute rejection) were present, this cell subset was undetectable in peripheral blood. In contrast the CD8+CD56+ T-cell subset was not discriminatory. The presence of CD4+CD56+ cells among freshly-isolated lymphocytes from renal allografts supports the idea that the local environment is involved in the selection of this subset, thus participating in the amplification of the immune-response. In addition, a homing of this T-cell subset into the transplanted organ may constitute an early sign of graft immunopathology.
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Seventy-seven T cell clones were generated from cell blasts infiltrating rejected kidney allografts. All clones, either CD4 or CD8, displayed cytolytic activity evaluated by lectin-dependent cell-mediated cytotoxicity (LDCC) and natural killer activities. Furthermore, both types of clones were able to produce IFN-gamma following PHA stimulation. These data suggest that the graft infiltrate is characterized by T cell clones with cytolytic potential responsible for the killing of graft cells. The production of IFN-gamma, enhancing the class II MHC expression, may amplify the recipient immune response.
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NK-1, NK-15 subsets and natural killer (NK) activity were studied in 13 patients, before undergoing renal transplantation and in the post-transplant period. Pretransplant there was a significant reduction of NK activity with a defect in Vmax capacity in all patients. NK-1+ and NK-15+ cell number was normal or slightly increased in all subjects. Post-transplant evaluation under cyclosporine immunosuppression showed a quantitative reduction in NK cells while no changes in NK activity and killing activity have been seen. We conclude that in spite of a numerical decrease, NK activity was not affected by cyclosporine treatment.