| Title | Characterization of a new regulatory CD4+ T cell subset in primary sjögren's syndrome |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2013 |
| Authors | Alunno, Alessia, Petrillo Maria Grazia, Nocentini Giuseppe, Bistoni Onelia, Bartoloni Elena, Caterbi Sara, Bianchini Rodolfo, Baldini Chiara, Nicoletti Ildo, Riccardi Carlo, and Gerli Roberto |
| Journal | Rheumatology (United Kingdom) |
| Volume | 52 |
| Pagination | 1387 – 1396 |
| Type of Article | Article |
| ISSN | 14620332 |
| Keywords | adult, article, Case-Control Studies, CD4+ CD25+ T lymphocyte, CD4+ T lymphocyte, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell expansion, cell infiltration, cell isolation, cell proliferation, Cells, clinical article, coculture, comparative study, controlled study, Cultured, disease activity, Disease Progression, Female, Flow cytometry, Fluorescent Antibody Technique, GITR, human, human cell, Humans, hydroxychloroquine, immunohistochemistry, in vitro study, inflammatory infiltrate, interleukin 10, Logistic Models, male, methotrexate, Middle Aged, Nonparametric, Phenotype, priority journal, real time polymerase chain reaction, Real-Time Polymerase Chain Reaction, Reference Values, Regulatory, regulatory T cells, salivary gland, Sjoegren syndrome, Sjogren's Syndrome, statistics, T-Lymphocyte Subsets, T-Lymphocytes, transcription factor FOXP3, transforming growth factor beta |
| Abstract | Objective. CD4+CD25lowGITR+ T lymphocytes expressing FoxP3 and showing regulatory function have been recently described in healthy donors (HD). The objective of the study was to investigate their presence and role in patients with primary SS (pSS). Methods. CD4+CD25lowGITR+ cells circulating in peripheral blood (PB) of patients with pSS were isolated by MACS technique, their phenotype was studied by flow cytometry and real-time PCR, and their function was studied by in vitro co-culture. CD4+CD25lowGITR+ cells infiltrating salivary glands (SGs) were revealed by immunohistochemistry. Results. Results indicated that conventional CD4+CD25high regulatory T cells (Tregs) are decreased, whereas CD4+CD25lowGITR+ cells are expanded in the PB of pSS as compared with HD. Phenotypic analysis demonstrated that CD4+CD25lowGITR+ cells display Treg markers, including FoxP3, TGF-β and IL-10, and functional experiments demonstrated that they exert a strong inhibitory activity against autologous effector cells. CD4+CD25lowGITR+ cells were detectable in great number in the SG inflammatory infiltrate. Interestingly, PB CD4+CD25lowGITR+ cell expansion was evident only in patients with inactive disease, while conventional CD4+CD25high Treg number was not associated with disease activity. Conclusion. The present data demonstrate that circulating CD4+ cells expressing GITR, but with low levels of CD25 (CD4+CD25lowGITR+), are detectable in pSS patients. These cells, displaying Treg phenotype and function, are present in SG inflamed tissues and are expanded in the PB of subjects with inactive disease. Data suggest that the expansion of CD4+CD25lowGITR+ cells in pSS may represent a counter-regulatory attempt against autoimmune-driven inflammation and may provide a new target for future treatment strategies. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. |
| Notes | Cited by: 53; All Open Access, Bronze Open Access |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880596163&doi=10.1093%2frheumatology%2fket179&partnerID=40&md5=c0fd2bca63ca5bf4d61179c94580dbdc |
| DOI | 10.1093/rheumatology/ket179 |
| Citation Key | Alunno20131387 |
| PubMed ID | 23674818 |
