دورية أكاديمية
A novel thymoma-associated immunodeficiency with increased naive T cells and reduced CD247 expression.
| العنوان: | A novel thymoma-associated immunodeficiency with increased naive T cells and reduced CD247 expression. |
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| المؤلفون: | Christopoulos P; Department of Pathology, University of Freiburg Medical Center, 79106 Freiburg, Germany;, Dopfer EP; Department of Molecular Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, University of Freiburg Medical Center, 79106 Freiburg, Germany; Center for Chronic Immunodeficiency CCI, University of Freiburg Medical Center, 79106 Freiburg, Germany; Max-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany;, Malkovsky M; Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726;, Esser PR; Department of Dermatology and Venereology (Allergy Research Group), University of Freiburg Medical Center, 79106 Freiburg, Germany;, Schaefer HE; Department of Pathology, University of Freiburg Medical Center, 79106 Freiburg, Germany;, Marx A; Institute of Pathology, University Medical Center Mannheim, 68167 Mannheim, Germany;, Kock S; Department of Pathology, University of Freiburg Medical Center, 79106 Freiburg, Germany;, Rupp N; Department of Pathology, University of Freiburg Medical Center, 79106 Freiburg, Germany;, Lorenz MR; Institute for Transfusion Medicine, University Ulm, 89081 Ulm, Germany;, Schwarz K; Institute for Transfusion Medicine, University Ulm, 89081 Ulm, Germany; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service, Baden-Württemberg-Hessen, 89081 Ulm, Germany;, Harder J; Department of Gastroenterology, University of Freiburg Medical Center, 79106 Freiburg, Germany; and., Martin SF; Department of Dermatology and Venereology (Allergy Research Group), University of Freiburg Medical Center, 79106 Freiburg, Germany;, Werner M; Department of Pathology, University of Freiburg Medical Center, 79106 Freiburg, Germany;, Bogdan C; Institute of Clinical Microbiology, Immunology and Hygiene, Friedrich Alexander University Erlangen-Nuremberg and University Hospital Erlangen, 91054 Erlangen, Germany., Schamel WW; Department of Molecular Immunology, BIOSS Centre for Biological Signalling Studies, Faculty of Biology, University of Freiburg Medical Center, 79106 Freiburg, Germany; Center for Chronic Immunodeficiency CCI, University of Freiburg Medical Center, 79106 Freiburg, Germany; Max-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany;, Fisch P; Department of Pathology, University of Freiburg Medical Center, 79106 Freiburg, Germany; paul.fisch@uniklinik-freiburg.de. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Apr 01; Vol. 194 (7), pp. 3045-53. Date of Electronic Publication: 2015 Mar 02. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Gene Expression Regulation*, CD3 Complex/*genetics , Immunologic Deficiency Syndromes/*genetics , Immunologic Deficiency Syndromes/*immunology , T-Lymphocyte Subsets/*immunology , T-Lymphocyte Subsets/*metabolism , Thymoma/*genetics , Thymoma/*immunology, Adult ; Antigens, Protozoan/immunology ; CD3 Complex/metabolism ; Cytokines/biosynthesis ; Exons ; Humans ; Immunologic Deficiency Syndromes/complications ; Immunologic Deficiency Syndromes/diagnosis ; Immunologic Memory ; Immunophenotyping ; Leishmania/immunology ; Lymphocyte Count ; Male ; Phenotype ; Primary Immunodeficiency Diseases ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Sequence Analysis, DNA ; Thymoma/complications ; Thymoma/diagnosis |
| مستخلص: | The mechanisms underlying thymoma-associated immunodeficiency are largely unknown, and the significance of increased blood γδ Τ cells often remains elusive. In this study we address these questions based on an index patient with thymoma, chronic visceral leishmaniasis, myasthenia gravis, and a marked increase of rare γδ T cell subsets in the peripheral blood. This patient showed cutaneous anergy, even though he had normal numbers of peripheral blood total lymphocytes as well as CD4(+) and CD8(+) T cells. Despite his chronic infection, analyses of immunophenotypes and spectratyping of his lymphocytes revealed an unusual accumulation of naive γδ and αβ T cells, suggesting a generalized T cell activation defect. Functional studies in vitro demonstrated substantially diminished IL-2 and IFN-γ production following TCR stimulation of his "untouched" naive CD4(+) T cells. Biochemical analysis revealed that his γδ and αβ T cells carried an altered TCR complex with reduced amounts of the ζ-chain (CD247). No mutations were found in the CD247 gene that encodes the homodimeric ζ protein. The diminished presence of CD247 and increased numbers of γδ T cells were also observed in thymocyte populations obtained from three other thymoma patients. Thus, our findings describe a novel type of a clinically relevant acquired T cell immunodeficiency in thymoma patients that is distinct from Good's syndrome. Its characteristics are an accumulation of CD247-deficient, hyporresponsive naive γδ and αβ T cells and an increased susceptibility to infections. (Copyright © 2015 by The American Association of Immunologists, Inc.) |
| التعليقات: | Comment in: J Immunol. 2015 Oct 15;195(8):3505. (PMID: 26432897) Comment in: J Immunol. 2015 Oct 15;195(8):3505-6. (PMID: 26432898) |
| المشرفين على المادة: | 0 (Antigens, Protozoan) 0 (CD3 Complex) 0 (CD3 antigen, zeta chain) 0 (Cytokines) 0 (Receptors, Antigen, T-Cell, alpha-beta) 0 (Receptors, Antigen, T-Cell, gamma-delta) |
| SCR Disease Name: | T cell immunodeficiency primary |
| تواريخ الأحداث: | Date Created: 20150304 Date Completed: 20150608 Latest Revision: 20191210 |
| رمز التحديث: | 20240628 |
| DOI: | 10.4049/jimmunol.1402805 |
| PMID: | 25732729 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.1402805 |