SYK expression endows human ZAP70-deficient CD8 T cells with residual TCR signaling

SYK expression endows human ZAP70-deficient CD8 T cells with residual TCR signaling

Copyright © 2015 Elsevier Inc. All rights reserved.

Détails bibliographiques
Publié dans:Clinical immunology (Orlando, Fla.). - 1999. - 161(2015), 2 vom: 17. Dez., Seite 103-9
Auteur principal: Hauck, Fabian (Auteur)
Autres auteurs: Blumenthal, Britta, Fuchs, Sebastian, Lenoir, Christelle, Martin, Emmanuel, Speckmann, Carsten, Vraetz, Thomas, Mannhardt-Laakmann, Wilma, Lambert, Nathalie, Gil, Marine, Borte, Stephan, Audrain, Marie, Schwarz, Klaus, Lim, Annick, Schamel, Wolfgang W, Fischer, Alain, Ehl, Stephan, Rensing-Ehl, Anne, Picard, Capucine, Latour, Sylvain
Format: Article en ligne
Langue:English
Publié: 2015
Accès à la collection:Clinical immunology (Orlando, Fla.)
Sujets:Journal Article Research Support, Non-U.S. Gov't CID Live vaccine adverse event SYK TCR signaling TREC newborn screening ZAP70 Intracellular Signaling Peptides and Proteins Receptors, Antigen, T-Cell plus... Protein-Tyrosine Kinases EC 2.7.10.1 SYK protein, human EC 2.7.10.2 Syk Kinase ZAP-70 Protein-Tyrosine Kinase ZAP70 protein, human
Description
Résumé:Copyright © 2015 Elsevier Inc. All rights reserved.
Autosomal recessive human ZAP70 deficiency is a rare cause of combined immunodeficiency (CID) characterized by defective CD4 T cells and profound CD8 T cell lymphopenia. Herein, we report two novel patients that extend the molecular genetics, the clinical and functional phenotypes associated with the ZAP70 deficiency. The patients presented as infant-onset CID with severe infections caused by varicella zoster virus and live vaccines. Retrospective TCR excision circle newborn screening was normal in both patients. One patient carried a novel non-sense mutation (p.A495fsX75); the other a previously described misense mutation (p.A507V). In contrast to CD4 T cells, the majority of the few CD8 T cells showed expression of the ZAP70-related tyrosine kinase SYK that correlated with residual TCR signaling including calcium flux and degranulation. Our findings highlight the differential requirements of ZAP70 and SYK during thymic development, peripheral homeostasis as well as effector functions of CD4 and CD8 T cells
Description:Date Completed 29.02.2016
Date Revised 26.11.2016
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2015.07.002