A Novel Thymoma-Associated Immunodeficiency with Increased Naive T Cells and Reduced CD247 Expression
| Autor: | Stefan F. Martin, Elaine P. Dopfer, Paul Fisch, Jan Harder, Martin Werner, Hans-Eckart Schaefer, Klaus Schwarz, Myriam Ricarda Lorenz, Nicole Rupp, Petros Christopoulos, Christian Bogdan, Philipp R. Esser, Miroslav Malkovsky, Sylvia Kock, Alexander Marx, Wolfgang W. A. Schamel |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Thymoma CD3 Complex Primary Immunodeficiency Diseases Receptors Antigen T-Cell alpha-beta T cell Immunology Antigens Protozoan Biology Immunophenotyping Interleukin 21 T-Lymphocyte Subsets medicine Humans Immunology and Allergy Cytotoxic T cell Lymphocyte Count Leishmania T-cell receptor Immunologic Deficiency Syndromes Receptors Antigen T-Cell gamma-delta Exons Sequence Analysis DNA medicine.disease Thymocyte Phenotype medicine.anatomical_structure Gene Expression Regulation Cytokines T-Cell Immunodeficiency Immunologic Memory CD8 |
| Zdroj: | The Journal of Immunology. 194:3045-3053 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|