Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients
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 counterpar...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/6637328 |
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| author | Ewa Kuca-Warnawin Magdalena Plebańczyk Krzysztof Bonek Ewa Kontny |
| author_facet | Ewa Kuca-Warnawin Magdalena Plebańczyk Krzysztof Bonek Ewa Kontny |
| author_sort | Ewa Kuca-Warnawin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-de562d64441a418b98479b23797be901 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-de562d64441a418b98479b23797be9012025-08-20T03:26:15ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/66373286637328Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis PatientsEwa Kuca-Warnawin0Magdalena Plebańczyk1Krzysztof Bonek2Ewa Kontny3Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, PolandDepartment of Rheumatology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, PolandBackground. 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.http://dx.doi.org/10.1155/2021/6637328 |
| spellingShingle | Ewa Kuca-Warnawin Magdalena Plebańczyk Krzysztof Bonek Ewa Kontny Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients Stem Cells International |
| title | Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients |
| title_full | Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients |
| title_fullStr | Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients |
| title_full_unstemmed | Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients |
| title_short | Inhibition of Allogeneic and Autologous T Cell Proliferation by Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients |
| title_sort | inhibition of allogeneic and autologous t cell proliferation by adipose derived mesenchymal stem cells of ankylosing spondylitis patients |
| url | http://dx.doi.org/10.1155/2021/6637328 |
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