A novel thymoma-associated immunodeficiency with increased naive T cells and reduced CD247 expression.
J Immunol
; 194(7): 3045-53, 2015 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-25732729
ABSTRACT
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 αß 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 αß 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 αß T cells and an increased susceptibility to infections.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Timoma
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Regulação da Expressão Gênica
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Subpopulações de Linfócitos T
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Complexo CD3
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Síndromes de Imunodeficiência
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2015
Tipo de documento:
Article