Gamma interferon activates a previously undescribed Ca2+ influx in T lymphocytes from patients with multiple sclerosis.
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. The etiology of the disease is still unknown. Activated T lymphocytes are considered essential in mediating the inflammatory process leading to demyelination in MS. They operate through a complex network of cytokines among which gamma interferon (gamma-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-mediated pathway, a previously undescribed gamma-IFN-activated Ca2+ influx, functionally coupled to the gamma-IFN receptor. The influx mainly expressed by CD4+ T lymphocytes, was found in 12 of 15 (80%) patients with clinically active MS and in 14 of 30 (46%) patients with stable 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 least part of gamma-IFN's contribution to the pathogenesis of MS is exerted through a Ca(2+)-dependent regulation of T lymphocyte activity.
Martino
G
G
Neuroimmunology Unit, University of Milan, San Rafaele Scientific Institute, Italy.
Clementi
E
E
Brambilla
E
E
Moiola
L
L
Comi
G
G
Meldolesi
J
J
Grimaldi
L M
LM
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D007371:Interferon-gamma; D011493:Protein Kinase C; D002118:Calcium