title: Uncoupling of T-cell antigen receptor and downstream protein tyrosine kinases in common variable immunodeficiency.
abstract: Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and the underlying mechanisms leading to the immunodeficiency. Although the overt defect is an impairment in B-cell function, there is increasing evidence of primary T-cell dysfunctions in a proportion of patients with CVID. We have analyzed T-cells from six CVID patients for activation of both early and late events in response to TCR triggering. The data showed that T-cells from three of six CVID patients were defective in the capacity to initiate the TCR/CD3 signaling pathway by activating intracellular tyrosine kinases, associated with impaired proliferative responses to TCR/CD3 triggering. Since both surface expression of the TCR/CD3 complex and intracellular expression of key tyrosine kinases such as p56lek and ZAP-70 were normal in these patients, our data suggest a defect in the earliest step of TCR signal transduction.
authors.affiliation: Department of Evolutionary Biology, University of Siena, Italy.
authors.forename: M B
authors.initials: MB
authors.lastname: Majolini
authors.forename: M M
authors.initials: MM
authors.lastname: D'Elios
authors.forename: M
authors.initials: M
authors.lastname: Boncristiano
authors.forename: P
authors.initials: P
authors.lastname: Galieni
authors.forename: G
authors.initials: G
authors.lastname: Del Prete
authors.forename: J L
authors.initials: JL
authors.lastname: Telford
authors.forename: C T
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D000328:Adult; D017074:Common Variable Immunodeficiency / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D008934:Mitogens; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases