The dysfunction of calcium-ATPase pump in double negative T cells of autoimmune-prone mice.
Double negative (DN) T cells expanding in peripheral lymphoid tissues in mice bearing lymphoproliferation (lpr) gene are generally unresponsive to mitogens, antigens, and anti-T cell receptor (TCR) or anti-CD3 monoclonal antibodies (mAb). In response to the stimulation with 0.125-5.0 microM ionomycin, control T cells sustained an increase in intracellular free calcium ([Ca2+]i), while DN lpr T cells showed a gradual fall following initial rapid increase in [Ca2+]i. Such gradual fall in [Ca2+]i was overcome by the addition of endoplasmic and sarcoplasmic reticulum Ca(2+)-ATPase inhibitor or high dose (10 microM) of ionomycin. The requirement of high concentration of calcium ionophore for the sustained increase of [Ca2+]i in lpr DN T cells is due to dysfunction of Ca(2+)-ATPase pump.
Wang
W
W
Section of Immunopathogenesis, Hokkaido University, Sapporo, Japan.
Kobayashi
S
S
Katagiri
Y
Y
Mori
K
K
Inobe
M
M
Uede
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000172:deficiency*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005260:Female; D016130:Immunophenotyping; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology*
D015759:Ionomycin; D000252:Calcium-Transporting ATPases; D002118:Calcium