Interferon-gamma-induced calcium influx in T lymphocytes of multiple sclerosis and rheumatoid arthritis patients: a complementary mechanism for T cell activation?
Autoreactive T lymphocytes are considered to play a crucial role in orchestrating a chronic inflammation in the central nervous system (CNS) of multiple sclerosis (MS) patients and in the joints of rheumatoid arthritis (RA) patients. However, it has been suggested that the majority of T cells in the immune infiltrate are nonspecifically recruited into the CNS and into the inflamed joint. In addition, several lines of evidence suggest an important role for interferon-gamma (IFN-gamma) in the pathogenesis of MS and RA. We have studied whether peripheral blood T cells from patients with autoimmune diseases are more susceptible to activation in the presence of IFN-gamma. The results indicate that IFN-gamma mediates a sustained elevated [Ca(2+)](i) in T cells of (active) MS and RA patients as compared to healthy controls and patients with common viral infections. No [Ca(2+)](i) increase was observed in Ca(2+)-free medium, excluding an effect of IFN-gamma on Ca(2+)-release from intracellular stores. Although the IFN-gamma-activated Ca(2+)-influx is insufficient to induce T cell proliferation in vitro, our data indicate a significantly augmented proliferation in response to suboptimal doses of PHA in the presence of IFN-gamma. This study suggests that the IFN-gamma-induced Ca(2+)-influx can act as a complementary mechanism in the activation of blood T lymphocytes from MS and RA patients.
Buntinx
Mieke
M
Biomedisch Onderzoeksinstituut, Limburgs Universitair Centrum and School of Life Sciences, Transnational University Limburg, Universitaire Campus gebouw A, B-3590 Diepenbeek, Belgium.
Ameloot
Marcel
M
Steels
Paul
P
Janssen
Paul
P
Medaer
Robert
R
Geusens
Piet
P
Raus
Jef
J
Stinissen
Piet
P
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D009994:Osmolar Concentration; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014777:Virus Diseases / Q000378:metabolism
D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D002118:Calcium