GAMMA-INTERFERON ACTIVATES A PREVIOUSLY UNDESCRIBED CA2-LYMPHOCYTES FROM PATIENTS WITH MULTIPLE-SCLEROSIS( INFLUX IN T)

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. The etiology of the disease is still unkn own. Activated T lymphocytes are considered essential in mediating the inflammatory process leading to demyelination of MS. They operate thr ough a complex network of cytokines among which gamma interferon (gamm a-IFN) plays a key role. Here we report that exposure to gamma-IFN of T lymphocytes from patients with MS activates, by a protein kinase C-m ediated pathway, a previously undescribed gamma-IFN-activated Ca2+ inf lux, functionally coupled to the gamma-IFN receptor. The influx, mainl y expressed by CD4(+) T lymphocytes, was found in 12 of 15 (80%) patie nts with clinically active MS and in 14 of 30 (46%) patients with stab le MS. The influx was found in only 3 of 24 (12%) control patients and in none of the 15 healthy subjects studied. Our results document the appearance in MS lymphocytes of a gamma-IFN-activated, protein kinase C-dependent, Ca2+ influx that might be due to the expression of a new cation-specific plasmalemma channel. This finding suggests that at lea st part of gamma-IFN's contribution to the pathogenesis of MS is exert ed through a Ca2+-dependent regulation of T lymphocyte activity.