γ interferon activates a previously undescribed Ca2+ influx in T lymphocytes from patients with multiple sclerosis

Gianvito Martino, Emilio Clementi, Elena Brambilla, Lucia Moiola, Giancarlo Comi, Jacopo Meldolesi, Luigi M E Grimaldi

Research output: Contribution to journalArticlepeer-review

Abstract

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 γ interferon (γ-IFN) plays a key role. Here we report that exposure to γ-IFN of T lymphocytes from patients with MS activates, by a protein kinase C-mediated pathway, a previously undescribed γ-IFN-activated Ca2+ influx, functionally coupled to the γ-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 γ-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 γ-IFN's contribution to the pathogenesis of MS is exerted through a Ca2+-dependent regulation of T lymphocyte activity.

Original languageEnglish
Pages (from-to)4825-4829
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number11
Publication statusPublished - May 24 1994

Keywords

  • Ca homeostasis
  • Cytokines
  • Protein kinase C

ASJC Scopus subject areas

  • General
  • Genetics

Fingerprint

Dive into the research topics of 'γ interferon activates a previously undescribed Ca2+ influx in T lymphocytes from patients with multiple sclerosis'. Together they form a unique fingerprint.

Cite this