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Comparing the Effec...
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Bergström, MarcusUppsala universitet,Klinisk immunologi
(författare)
Comparing the Effects of the mTOR Inhibitors Azithromycin and Rapamycin on In Vitro Expanded Regulatory T Cells
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
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2019-09-12
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SAGE PUBLICATIONS INC,2019
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-408845
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-408845URI
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https://doi.org/10.1177/0963689719872488DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Adoptive transfer of autologous polyclonal regulatory T cells (Tregs) is a promising option for reducing graft rejection in allogeneic transplantation. To gain therapeutic levels of Tregs there is a need to expand obtained cells ex vivo, usually in the presence of the mTOR inhibitor Rapamycin due to its ability to suppress proliferation of non-Treg T cells, thus promoting a purer Treg yield. Azithromycin is a bacteriostatic macrolide with mTOR inhibitory activity that has been shown to exert immunomodulatory effects on several types of immune cells. In this study we investigated the effects of Azithromycin, compared with Rapamycin, on Treg phenotype, growth, and function when expanding bulk, naive, and memory Tregs. Furthermore, the intracellular concentration of Rapamycin in CD4+ T cells as well as in the culture medium was measured for up to 48 h after supplemented. Treg phenotype was assessed by flow cytometry and Treg function was measured as inhibition of responder T-cell expansion in a suppression assay. The concentration of Rapamycin was quantified with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Azithromycin and Rapamycin both promoted a FoxP3-positive Treg phenotype in bulk Tregs, while Rapamycin also increased FoxP3 and FoxP3+Helios positivity in naive and memory Tregs. Furthermore, Rapamycin inhibited the expansion of naive Tregs, but also increased their suppressive effect. Rapamycin was quickly degraded in 37 degrees C medium, yet was retained intracellularly. While both compounds may benefit expansion of FoxP3+ Tregs in vitro, further studies elucidating the effects of Azithromycin treatment on Tregs are needed to determine its potential use.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Müller, MalinUppsala universitet,Klinisk immunologi(Swepub:uu)malmu262
(författare)
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Karlsson, MarieUppsala universitet,Klinisk immunologi(Swepub:uu)makar254
(författare)
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Scholz, HanneOslo Univ Hosp, Dept Transplant Med, Oslo, Norway;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway;Univ Oslo, Ctr Excellence, Inst Basic Med Sci, Hybrid Technol Hub, Oslo, Norway
(författare)
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Vethe, Nils ToreOslo Univ Hosp, Dept Pharmacol, Oslo, Norway
(författare)
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Korsgren, OlleUppsala universitet,Klinisk immunologi(Swepub:uu)ollekors
(författare)
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Uppsala universitetKlinisk immunologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cell Transplantation: SAGE PUBLICATIONS INC28:12, s. 1603-16130963-68971555-3892
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