Defective T cell Fas function in patients with multiple sclerosis

Citation
C. Comi et al., Defective T cell Fas function in patients with multiple sclerosis, NEUROLOGY, 55(7), 2000, pp. 921-927
Citations number
46
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
NEUROLOGY
ISSN journal
00283878 → ACNP
Volume
55
Issue
7
Year of publication
2000
Pages
921 - 927
Database
ISI
SICI code
0028-3878(20001010)55:7<921:DTCFFI>2.0.ZU;2-G
Abstract
Background; Fas (CD95) triggers programmed cell death and is involved in sh utting off the immune response. Inherited deleterious mutations hitting Fas or its signaling pathway cause autoimmune/lymphoproliferative syndrome (AL PS). Objective: To assess the possibility that decreased Fas function plays a role in development of MS. Methods: The authors evaluated Fas function i n long-term T cell lines (21 days of culture) from 32 patients with relapsi ng-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 15 wit h primary progressive MS (PPMS) by assessing cell survival upon Fas trigger ing by monoclonal antibodies (Mab). Results: Fas-induced cell death was sig nificantly lower in all patient groups than in controls, and lower in SPMS than in RRMS. Moreover, 8/15 patients with PPMS, 10/15 with SPMS, and 8/32 with RRMS were frankly resistant to Fas. Frequency of resistance to Fas-ind uced cell death was significantly higher in all patient groups than in cont rols (2/75), and higher in SPMS than in RRMS. The findings that the parents of two Fas-resistant patients were Fas-resistant and that fusion of T cell s from two Fas-resistant patients with Fas-sensitive HUT78 cells gave rise to Fas-resistant hybrid lines suggest that Fas-resistance is due to inherit ed alterations of the Fas signaling pathway, with production of molecules e xerting a dominant negative effect on a normal Fas system. Conclusions: Def ects of the immune response shutting-off system may be involved in the path ogenesis of MS, particularly in its progressive evolution.