| Title | Expansion of regulatory GITR+CD25low/-CD4+ T cells in systemic lupus erythematosus patients |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 2014 |
| Authors | Nocentini, Giuseppe, Alunno Alessia, Petrillo Maria Grazia, Bistoni Onelia, Bartoloni Elena, Caterbi Sara, Ronchetti Simona, Migliorati Graziella, Riccardi Carlo, and Gerli Roberto |
| Journal | Arthritis Research and Therapy |
| Volume | 16 |
| Pagination | 1 – 15 |
| Type of Article | Article |
| ISSN | 14786354 |
| Keywords | adult, article, blood, CD4+ T lymphocyte, cell contact, Cell expansion, cell isolation, cell population, cell proliferation, clinical article, controlled study, cytology, cytotoxic T lymphocyte antigen 4, Female, Flow cytometry, glucocorticoid induced tumor necrosis factor receptor, Glucocorticoid-Induced TNFR-Related Protein, human, human cell, Humans, IL2RA protein, immune response, immunology, Immunophenotyping, interleukin 10, interleukin 2 receptor alpha, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Lymphocyte Count, male, metabolism, Middle Aged, peripheral blood mononuclear cell, Phenotype, Regulatory, regulatory T lymphocyte, Systemic, systemic lupus erythematosus, T-Lymphocytes, Tnfrsf18 protein, transcription factor FOXP3, transforming growth factor beta |
| Abstract | Introduction: CD4+CD25low/-GITR+ T lymphocytes expressing forkhead box protein P3 (FoxP3) and showing regulatory activity have been recently described in healthy donors. The objective of the study was to evaluate the proportion of CD4+CD25low/-GITR+ T lymphocytes within CD4+ T cells and compare their phenotypic and functional profile with that of CD4+CD25highGITR- T lymphocytes in systemic lupus erythematosus (SLE) patients. Methods: The percentage of CD4+CD25low/-GITR+ cells circulating in the peripheral blood (PB) of 32 patients with SLE and 25 healthy controls was evaluated with flow cytometry. CD4+CD25low/-GITR+ cells were isolated with magnetic separation, and their phenotype was compared with that of CD4+CD25highGITR- cells. Regulatory activity of both cell subsets was tested in autologous and heterologous co-cultures after purification through a negative sorting strategy. Results: Results indicated that CD4+CD25low/-GITR+ cells are expanded in the PB of 50% of SLE patients. Expansion was observed only in patients with inactive disease. Phenotypic analysis demonstrated that CD4+CD25low/-GITR+ cells display regulatory T-cell (Treg) markers, including FoxP3, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), transforming growth factor-beta (TGF-β), and interleukin (IL)-10. In contrast, CD4+CD25highGITR- cells appear to be activated and express low levels of Treg markers. Functional experiments demonstrated that CD4+CD25low/-GITR+ cells exert a higher inhibitory activity against both autologous and heterologous cells as compared with CD4+CD25highGITR- cells. Suppression is independent of cell contact and is mediated by IL-10 and TGF-β. Conclusions: Phenotypic and functional data demonstrate that in SLE patients, CD4+CD25low/-GITR+ cells are fully active Treg cells, possibly representing peripheral Treg (pTreg) that are expanded in patients with inactive disease. These data may suggest a key role of this T-cell subset in the modulation of the abnormal immune response in SLE. Strategies aimed at expanding this Treg subset for therapeutic purpose deserve to be investigated. © 2014 Nocentini et al. |
| Notes | Cited by: 38; All Open Access, Gold Open Access, Green Open Access |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84990882590&doi=10.1186%2fs13075-014-0444-x&partnerID=40&md5=084f63ba8f87b3049ff950053538ad1c |
| DOI | 10.1186/s13075-014-0444-x |
| Citation Key | Nocentini20141 |
| PubMed ID | 25256257 |
