title: Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase.
abstract: We have previously described a type of selective T cell deficiency (STD) characterized by persistent infections reminiscent of severe combined immunodeficiency. We show here that STD patients carry a mutation of zap-70, resulting in loss of the activity of this kinase. The thymi of zap-70-/- patients show the presence of CD4+CD8+ cells in the cortex; however, only CD4, not CD8, single-positive cells are present in the medulla. Peripheral CD4+ T cells from the zap-70-/- patients exhibit markedly reduced tyrosine phosphorylation, fail to produce interleukin-2, and do not proliferate in response to T cell receptor stimulation by mitogens or antigens. Thus, Zap-70 kinase appears to be indispensable for the development of CD8 single-positive T cells as well as for signal transduction and function of single-positive CD4 T cells.
authors.affiliation: Division of Immunology and Allergy, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Arpaia
authors.forename: M
authors.initials: M
authors.lastname: Shahar
authors.forename: H
authors.initials: H
authors.lastname: Dadi
authors.forename: A
authors.initials: A
authors.lastname: Cohen
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000595:Amino Acid Sequence; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D006579:Heterozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology; D013950:Thymus Gland / Q000166:cytology*; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human