A primary XXXX associated with defective transmembrane calcium influx.

@entity1 @entity2803 @entity14634 @entity2426 @entity55 @entity141 @entity294 @entity3138 @entity2952 @entity7984 @entity1199 @entity669
We investigated a T-cell activation deficiency in a 3-month-old @entity1 with @entity294 , serious @entity55 , and a family history (in a brother) of @entity2803 . In spite of detection of normal number of peripheral lymphocytes, T cells did not proliferate after activation by anti-CD3 and anti- @entity3138 antibodies, although proliferation induced by antigens was detectable. We sought to determine the origin of this defect as it potentially represented a valuable tool to analyze T-cell physiology. T-cell activation by anti-CD3 antibody or phytohemagglutinin (PHA) led to reduced @entity1199 ( @entity1199 ) production and abnormal nuclear factor-activated T cell (NF-AT; a complex regulating the @entity1199 gene transcription) binding activity to a specific oligonucleotide. T-cell proliferation was restored by @entity1199 . Early events of T-cell activation, such as anti-CD3 antibody-induced cellular protein @entity669 phosphorylation, @entity7984 and @entity2952 kinase activities, and phosphoinositide turnover, were found to be normal. In contrast, anti-CD3 antibody-induced @entity141 flux was grossly abnormal. Release from endoplasmic reticulum stores was detectable as tested in the presence of anti-CD3 antibody or @entity2426 after cell membrane depolarization in a K+ rich medium, whereas extracellular entry of @entity141 was defective. The latter abnormality was not secondary to defective K+ channel function, which was found to be normal. A similar defect was found in other hematopoietic cell lineages and in fibroblasts as evaluated by both cytometry and digital video imaging experiments at a single-cell level. This primary @entity14634 appears, thus, to be due to defective @entity141 entry through the plasma membrane. The same abnormality did not alter B-cell proliferation, platelet function, and polymorphonuclear neutrophil (PMN) function. Elucidation of the mechanism underlying this defect would help to understand the physiology of @entity141 mobilization in T cells.
