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Sunil Chauhan, Masahiro Omoto; Interface between Mesenchymal Stem Cells and Regulatory T Cell. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):868.
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© ARVO (1962-2015); The Authors (2016-present)
While mesenchymal stem cells (MSC) and regulatory T cells (Tregs) are immunomodulatory in their own right, MSCs can also enhance the suppressive function of Tregs to efficiently regulate the host immune response. However, the mechanisms how MSCs and Tregs interact are unclear. The purpose of this study was to investigate the mechanisms of MSC-Treg interaction, and its effect on Treg function.
Naïve Balb/c mice were used to generate bone marrow-derived MSCs (CD45-CD34-SCA1+ CD29+), and to isolate CD4+CD25+ Tregs (purity: >95% Foxp3+) from spleen and lymph nodes. MSCs and purified Tregs were co-cultured with or without transwells (1 mm pore size). After 72h, Tregs (CD4+CD25+Foxp3+) were assessed by flow cytometry, or live Tregs were sorted to quantify Foxp3 protein level using ELISA. MSC expression of CD80 was investigated using flow cytometry. The effect of blocking MSC-expressed CD80 on Treg suppressive function was analyzed using CD80 blocking antibodies.<br /> <!--[endif]-->
Flow cytometry and ELISA analyses showed that Tregs co-cultured with MSCs either in direct cell-to-cell contact or in transwells expressed significantly increased (2-3 fold) levels of Foxp3 compared with Tregs cultured without MSCs (p<0.01). However, MSCs were more effective in amplifying Treg- expression of Foxp3 when co-cultured in direct contact with Tregs than in transwells (p<0.02). All MSCs expressed CD80, and addition of anti-CD80 antibodies in a MSC-Treg co-culture assay significantly reduced the suppressive function of Tregs (~35%, p<0.02).
Our results demonstrate that direct cell-to-cell interaction between MSCs and Tregs is essential for maximal enhancement of Treg function, which in part is mediated by MSC-expressed CD80 molecule.
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