Expansions of salivary gland CD4+ T cells from Sjögren’s syndrome patients: single-cell repertoire analysis and correlation with clinical measures of disease (HUM3P.255)
| Autor: | Michelle Joachims, Kerry Leehan, Christina Lawrence, Zijian Pan, Lida Radfar, Astrid Rasmussen, R. Scofield, Kathy Sivils, Linda Thompson, A. Farris |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 194:121.15-121.15 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Sjögren’s syndrome is a systemic rheumatic disorder characterized by dry eyes, dry mouth and T cell infiltration of exocrine gland tissue. To determine the extent of salivary gland (SG) CD4+ memory T cell clonal expansion and whether these expansions are as frequent in peripheral blood (PB), a multiplex PCR method was used to amplify both the α and β T cell receptor (TCR) sequences from memory CD4+ T cells sorted from SG lip biopsy tissue and PB of 10 primary Sjögren’s syndrome patients. Over 3,000 TCR sequences were obtained from 50-115 (median 91) individual SG and 75-121 (median 104) individual PB T cells per patient. The percentage of cells that were part of clonal expansions was significantly higher in SG (median 11%, range 0-28%) compared to PB (median 0.9%, range 0-7%, p=0.003). Sequence analysis revealed: 1) highly homologous CDR3s among different expanded SG T cell clones within single patients, suggesting antigen-driven expansion and 2) unique cases of convergent recombination among unrelated patients, where different V segments/additions/deletions were utilized to make identical CDR3 amino acid sequences. The percentages of clonally expanded SG T cells correlated significantly with degree of SG fibrosis and reduced saliva production but not with systemic features of disease. SG clonal expansions detected in this study likely identify T cells involved in recognition of common antigen(s) and glandular dysfunction. |
| Databáze: | OpenAIRE |
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