SYK expression endows human ZAP70-deficient CD8 T cells with residual TCR signaling
| Autor: | Annick Lim, Nathalie Lambert, Christelle Lenoir, Anne Rensing-Ehl, Stephan Ehl, Carsten Speckmann, Sebastian Fuchs, Wilma Mannhardt-Laakmann, Klaus Schwarz, Wolfgang W. A. Schamel, Capucine Picard, Fabian Hauck, Britta Blumenthal, Marine Gil, Thomas Vraetz, Sylvain Latour, Alain Fischer, Stephan Borte, Marie Audrain, Emmanuel Martin |
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| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Immunology ZAP70 deficiency Receptors Antigen T-Cell Syk CD8-Positive T-Lymphocytes Biology Calcium flux medicine Humans Syk Kinase Immunology and Allergy Cytotoxic T cell Immunodeficiency Retrospective Studies ZAP-70 Protein-Tyrosine Kinase ZAP70 T-cell receptor Immunologic Deficiency Syndromes Intracellular Signaling Peptides and Proteins Degranulation Infant Protein-Tyrosine Kinases medicine.disease Child Preschool Mutation Cancer research Severe Combined Immunodeficiency Signal Transduction |
| Zdroj: | Clinical Immunology. 161:103-109 |
| ISSN: | 1521-6616 |
| DOI: | 10.1016/j.clim.2015.07.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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