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Transforming growth factor-β2 increases the capacity of retinal pigment epithelial cells to induce the generation of regulatory T cells.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2016 Feb; Vol. 13 (2), pp. 1367-72. Date of Electronic Publication: 2015 Dec 09. - Publication Year :
- 2016
-
Abstract
- The present study investigated the underlying mechanism of the induction of regulatory T cells (Tregs) by retinal pigment epithelial (RPE) cells and the characteristics of these Tregs. Human RPE cells were cultured in the presence or absence of transforming growth factor-β 2 (TGF-β2), and reverse-transcription quantitative PCR was performed to determine the mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear factor erythroid 2-related factor (Nrf2). Supernatants of RPE cell cultures were added to CD4+ T cells to induce Tregs. The RPE-induced Tregs were purified by two-step magnetic cell sorting. The natural Tregs were isolated from the peripheral blood mononuclear cells of healthy volunteers. Purified CD4+ CD25- T cells (2 x 10(5)/well) were cultured alone or with Tregs (various densities, natural or RPE-induced). The proliferation of CD4+ CD25- T cells was determined by 3H-thymidine incorporation. After 24 h of stimulation with TGF-β2, the mRNA expression of IDO in RPE cells was upregulated. The highest level of IDO mRNA expression was reached after 72 h of stimulation with TGF-β2. However, the Nrf2 mRNA expression was slightly decreased after 24 h of stimulation with TGF-β2 and significantly increased after 48-72 h of TGF-β2 stimulation. Increased levels of CD25 expression were observed on CD4+ T cells exposed to supernatants of RPE cell cultures treated with TGF-β2 and recombinant interleukin-2. The RPE-induced Tregs were more effective at suppressing the proliferation of CD4+ CD25- T cells compared with native Tregs. These findings suggested that IDO may be a signaling protein in RPE cells which is implicated in the induction of Tregs. RPE-induced Tregs have the potential to be applied for immunotherapy for ocular inflammatory diseases.
- Subjects :
- Cell Differentiation drug effects
Cell Line
Cell Proliferation drug effects
Cell Separation
Epithelial Cells drug effects
Flow Cytometry
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Lymphocyte Activation drug effects
NF-E2-Related Factor 2 metabolism
Phenotype
RNA, Messenger genetics
RNA, Messenger metabolism
T-Lymphocytes, Regulatory drug effects
Up-Regulation drug effects
Epithelial Cells metabolism
Retinal Pigment Epithelium cytology
T-Lymphocytes, Regulatory metabolism
Transforming Growth Factor beta2 pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 26676103
- Full Text :
- https://doi.org/10.3892/mmr.2015.4666