Limited heterogeneity of biased T‐cell receptor Vβ gene usage in lung but not blood T cells in active pulmonary sarcoidosis
| Autor: | Ronald G. Crystal, R. F. Silver, D. R. Moller |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Receptors Antigen T-Cell alpha-beta Molecular Sequence Data Immunology Biology Polymerase Chain Reaction Sarcoidosis Pulmonary medicine Humans Immunology and Allergy Gene family Nucleotide Amino Acid Sequence Receptor Lung Gene chemistry.chemical_classification Base Sequence T-cell receptor medicine.disease Amino acid medicine.anatomical_structure chemistry Female Sarcoidosis Bronchoalveolar Lavage Fluid Research Article |
| Zdroj: | Immunology. 88:516-523 |
| ISSN: | 1365-2567 0019-2805 |
| Popis: | Sarcoidosis is a multisystem disorder characterized by non-caseating granulomas and the accumulation of CD4+ T cells in involved tissues such as the lung. To evaluate the diversity of the CD4+ T-cell repertoire in this disorder, a detailed clonal analysis was performed in five individuals with active sarcoidosis who demonstrated preferential accumulation of T cells expressing the T-cell receptor variable gene family V beta 8 in either the lung or blood. In three individuals, analysis of unselected samples of nucleotide sequences derived from V beta 8+ lung T cells demonstrated degrees of clonality ranging from 11% to 46%, indicating the expansion of limited numbers of V beta 8+ T-cell clones in the lung. Analysis of the corresponding deduced amino acid sequences demonstrated common VDJ junctional amino acid residues in the dominant V beta 8+ T-cell clones derived from two oligoclonal V beta 8+ lung T-cell populations, consistent with an antigen-specific T-cell response. In contrast, analysis of V beta 8+ CD4+ T cells from the blood of an individual with a marked bias for peripheral blood V beta 8+ T cells demonstrated no evidence of oligoclonality, suggesting that the stimulus for circulating biased V beta-specific T cells in sarcoidosis may derive from a different, perhaps superantigenic, origin. Clinical improvement in the disease either in response to treatment with corticosteroids or as a result of spontaneous resolution was associated with a decrease in the proportion of V beta 8-specific T cells in the biased lung and/or blood T-cell compartments. Together, these observations are consistent with a role for this T-cell subset in the clinical manifestations of active granulomatous disease. |
| Databáze: | OpenAIRE |
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