OBJECTIVE: T cell activation plays a pivotal role in the immunopathogenesis of systemic sclerosis (SSc). Lymphocyte processes are tightly controlled by molecules activating either proliferation or programmed cell death (apoptosis). We investigated whether an imbalance in apoptotic function, increasing the survival rate of autoreactive cells, may lead to persistent autoreactive phenomena. METHODS: We studied peripheral a/b and g/d T lymphocytes of 22 patients with SSc and 22 healthy controls for their spontaneous and stimulated (phytohemagglutinin, dexamethasone) apoptotic rate and surface phenotype including expression of Fas (CD95) and Bcl-2, determined by flow cytometry. sFas and sFas ligand in sera and supernatants were measured by ELISA. Caspase-3 activation in response to agonistic anti-Fas Mab treatment was assessed. RESULTS: Lymphocytes of SSc patients showed a significant decrease in the percentage of apoptotic cells over time, in both unstimulated and stimulated cultures, compared to controls. We observed no difference between patients and controls, in stimulated or unstimulated cells, in the phenotypic expression of apoptotic cells, including surface Fas. SSc T cells were less susceptible to undergoing apoptosis after anti-Fas stimulation. We observed a significant decrease of apoptotic cells from stimulated culture of isolated SSc g/d T cells. Serum levels of sFas in SSc patients were significantly higher compared to controls. Similar data were obtained in the supernatants of stimulated and unstimulated cultures. By contrast, sFas ligand was always reduced. Bcl-2 expression in SSc was significantly elevated. A significant decrease in caspase-3 activity was detected in SSc patients after treatment by agonistic anti-Fas antibody. CONCLUSION: Resistance to apoptosis is present in a/b and g/d T cell lymphocyte subsets of patients with SSc, and several pathways seem to be connected in this setting.
OBJECTIVE: T cell activation plays a pivotal role in the immunopathogenesis of systemic sclerosis (SSc). Lymphocyte processes are tightly controlled by molecules activating either proliferation or programmed cell death (apoptosis). We investigated whether an imbalance in apoptotic function, increasing the survival rate of autoreactive cells, may lead to persistent autoreactive phenomena. METHODS: We studied peripheral a/b and g/d T lymphocytes of 22 patients with SSc and 22 healthy controls for their spontaneous and stimulated (phytohemagglutinin, dexamethasone) apoptotic rate and surface phenotype including expression of Fas (CD95) and Bcl-2, determined by flow cytometry. sFas and sFas ligand in sera and supernatants were measured by ELISA. Caspase-3 activation in response to agonistic anti-Fas Mab treatment was assessed. RESULTS: Lymphocytes of SSc patients showed a significant decrease in the percentage of apoptotic cells over time, in both unstimulated and stimulated cultures, compared to controls. We observed no difference between patients and controls, in stimulated or unstimulated cells, in the phenotypic expression of apoptotic cells, including surface Fas. SSc T cells were less susceptible to undergoing apoptosis after anti-Fas stimulation. We observed a significant decrease of apoptotic cells from stimulated culture of isolated SSc g/d T cells. Serum levels of sFas in SSc patients were significantly higher compared to controls. Similar data were obtained in the supernatants of stimulated and unstimulated cultures. By contrast, sFas ligand was always reduced. Bcl-2 expression in SSc was significantly elevated. A significant decrease in caspase-3 activity was detected in SSc patients after treatment by agonistic anti-Fas antibody. CONCLUSION: Resistance to apoptosis is present in a/b and g/d T cell lymphocyte subsets of patients with SSc, and several pathways seem to be connected in this setting.
Authors: Suleyman Serdar Koca; Metin Ozgen; Ferda Dagli; Mehmet Tuzcu; Ibrahim Hanifi Ozercan; Kazim Sahin; Ahmet Isik Journal: Inflammation Date: 2012-06 Impact factor: 4.092
Authors: P Cipriani; P Di Benedetto; V Liakouli; B Del Papa; M Di Padova; M Di Ianni; A Marrelli; E Alesse; R Giacomelli Journal: Clin Exp Immunol Date: 2013-08 Impact factor: 4.330
Authors: Ankoor Shah; Jan Storek; Rob Woolson; Ashley Pinckney; Lynnette Keyes-Elstein; Paul K Wallace; Gregory D Sempowski; Peter McSweeney; Maureen D Mayes; Leslie Crofford; M E Csuka; Kristine Phillips; Dinesh Khanna; Robert Simms; Karen Ballen; Sharon LeClercq; William St Clair; Andrew B Nixon; Richard Nash; Mark Wener; Richard Brasington; Richard Silver; Linda M Griffith; Daniel E Furst; Ellen Goldmuntz; Keith M Sullivan Journal: Rheumatology (Oxford) Date: 2022-10-06 Impact factor: 7.046
Authors: José Manuel López-Cacho; Soledad Gallardo; Manuel Posada; Miriam Aguerri; David Calzada; Teodoro Mayayo; María Luisa González-Rodríguez; Antonio María Rabasco; Carlos Lahoz; Blanca Cárdaba Journal: Biomed Res Int Date: 2014-04-10 Impact factor: 3.411