Helios, CD73 and CD39 Induction in Regulatory T Cells Exposed to Adipose Derived Mesenchymal Stem Cells

Fakhimi, Maryam; Talei, Abdol-Rasoul; Ghaderi, Abbas; Habibagahi, Mojtaba; Razmkhah, Mahboobeh

doi:10.22074/cellj.2020.6313

Helios, CD73 and CD39 Induction in Regulatory T Cells Exposed to Adipose Derived Mesenchymal Stem Cells

Document Type : Original Article

Authors

¹ .Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran ;.Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

² .Breast Diseases Research Center (BDRC), Shiraz University of Medical Sciences, Shiraz, Iran

³ .Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

⁴ .Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

10.22074/cellj.2020.6313

Abstract

Objective
Mesenchymal stem cells (MSCs) have prominent immunomodulatory roles in the tumor microenvironment. The current study intended to elucidate Treg subsets and their cytokines after exposing naïve T lymphocytes to adipose- derived MSCs (ASCs).
Materials and Methods
In this experimental study, to obtain ASCs, breast adipose tissues of a breast cancer patient and a normal individual were used. Magnetic cell sorting (MACS) was employed for purifying naïve CD4+T cells from peripheral blood of five healthy donors. Naïve CD4+T cells were then co-cultured with ASCs for five days. The phenotype of regulatory T cells (Tregs) and production of interleukine-10 (IL-10), transforming growth factor beta (TGF-β) and IL-17 were assessed using flow cytometry and ELISPOT assays, respectively.
Results
CD4+CD25-FOXP3+CD45RA+Tregs were expanded in the presence of cancer ASCs but CD4+CD25+Foxp3+CD45RA+regulatory T cells were up-regulated in the presence of both cancer- and normal-ASCs. This up-regulation was statistically significant in breast cancer-ASCs compared to the cells cultured without ASCs (P=0.002). CD4+CD25+ FOXP3+Helios+, CD4+CD25-FOXP3+Helios+and CD25+FOXP3+CD73+CD39+Tregs were expanded after co-culturing of T cells with both cancer-ASCs and normal-ASCs, while they were statistically significant only in the presence of cancer-ASCs (P < 0.05). Production of IL-10, IL-17 and TGF-β by T cells was increased in the presence of either normal- or cancer-ASCs; however, significant effect was only observed in the IL-10 and TGF-β of cancer-ASCs (P < 0.05).
Conclusion
The results further confirm the immunosuppressive impacts of ASCs on T lymphocytes and direct them to specific regulatory phenotypes which may support immune evasion and tumor growth.

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