Dataset Information

Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients.

ABSTRACT:

Background

In ankylosing spondylitis (AS), accompanied by chronic inflammation, T cell expansion plays a pathogenic role; the immunoregulatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) are impaired, while functional characteristics of their adipose tissue-derived counterparts are (ASCs) unknown.

Methods

We evaluated the antiproliferative activity of AS/ASCs, obtained from 20 patients, towards allogeneic and autologous T lymphocytes, using ASCs from healthy donors (HD/ASCs) as the reference cell lines. The PHA-activated peripheral blood mononuclear cells (PBMCs) were cocultured in cell-cell contact and transwell conditions with untreated or TNF + IFNγ- (TI-) licensed ASCs, then analyzed by flow cytometry to identify proliferating and nonproliferating CD4⁺ and CD8⁺ T cells. The concentrations of kynurenines, prostaglandin E₂ (PGE₂), and IL-10 were measured in culture supernatants.

Results

In an allogeneic system, HD/ASCs and AS/ASCs similarly decreased the proliferation of CD4⁺ and CD8⁺ T cells and acted mainly via soluble factors. The concentrations of kynurenines and PGE₂ inversely correlated with T cell proliferation, and selective inhibitors of these factors synthesis significantly restored T cell response. AS/ASCs exerted a similar antiproliferative impact also on autologous T cells.

Conclusion

We report for the first time that despite chronic in vivo exposure to inflammatory conditions, AS/ASCs retain the normal capability to restrain expansion of allogeneic and autologous CD4⁺ and CD8⁺ T cells, act primarily via kynurenines and PGE₂, and thus may have potential therapeutic value. Some distinctions between the antiproliferative effects of AS/ASCs and HD/ASCs suggest in vivo licensing of AS/ASCs.

SUBMITTER: Kuca-Warnawin E

PROVIDER: S-EPMC7979299 | biostudies-literature |

REPOSITORIES: biostudies-literature

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