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

被引：23

作者：

Hauck, Fabian ^{[1
,2
]}

Blumenthal, Britta ^{[4
,5
]}

Fuchs, Sebastian ^{[5
,6
]}

Lenoir, Christelle ^{[2
]}

Martin, Emmanuel ^{[2
]}

Speckmann, Carsten ^{[5
,7
]}

Vraetz, Thomas ^{[7
]}

Mannhardt-Laakmann, Wilma ^{[8
]}

Lambert, Nathalie ^{[9
]}

Gil, Marine ^{[9
]}

Borte, Stephan ^{[10
,11
]}

Audrain, Marie ^{[12
]}

Schwarz, Klaus ^{[13
,14
]}

Lim, Annick ^{[15
]}

Schamel, Wolfgang W. ^{[4
,5
]}

Fischer, Alain ^{[2
,3
,16
,17
]}

Ehl, Stephan ^{[5
,7
]}

Rensing-Ehl, Anne ^{[5
]}

Picard, Capucine ^{[3
,9
,18
]}

Latour, Sylvain ^{[2
,3
]}

机构：

[1] Univ Munich, Dr von Hauner Childrens Hosp, Munich, Germany

[2] Inst IMAGINE, Lab Lymphocyte Activat & Susceptibil EBV Infect, INSERM UMR1163, F-75015 Paris, France

[3] Paris Descartes Univ, Imagine Inst, Sorbonne Paris Cite, Paris, France

[4] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Fac Biol, D-79106 Freiburg, Germany

[5] Univ Freiburg, Univ Med Ctr, CCI, D-79106 Freiburg, Germany

[6] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany

[7] Univ Freiburg, Ctr Pediat & Adolescent Med, Univ Med Ctr, D-79106 Freiburg, Germany

[8] Univ Hosp Mainz, Div Pediat Immunol & Rheumatol, Dept Pediat, Mainz, Germany

[9] Hop Necker Enfants Malad, Study Ctr Immunodeficiencies, AP HP, Paris, France

[10] St Georg Hosp, ImmunoDeficiencyCtr Leipzig IDCL, Leipzig, Germany

[11] Univ Leipzig, Translat Ctr Regenerat Med TRM, D-04109 Leipzig, Germany

[12] CHU Nantes, Lab Immunol, Nantes, France

[13] Univ Hosp Ulm, Inst Transfus Med, Ulm, Germany

[14] German Red Cross Blood Serv, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany

[15] Inst Pasteur, Unite Regulat Immunitaire & Vaccinol, Paris, France

[16] Hop Necker Enfants Malad, Unite Immunol & Hematol Pediat, AP HP, Paris, France

[17] Coll France, F-75231 Paris, France

[18] Necker Med Sch, Inst IMAGINE, Necker Branch, Lab Human Genet Infect Dis,INSERM UMR 1163, Paris, France

来源：

CLINICAL IMMUNOLOGY | 2015年 / 161卷 / 02期

基金：

欧洲研究理事会;

关键词：

CID; ZAP70; SYK; TCR signaling; TREC newborn screening; Live vaccine adverse event; PROTEIN-TYROSINE KINASE; ZAP-70-DEFICIENT PATIENTS; ANTIGEN RECEPTOR; ZAP-70; ZAP70; IMMUNODEFICIENCY; PHOSPHORYLATION; SELECTION;

D O I：

10.1016/j.clim.2015.07.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：103 / 109

页数：7

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