Calcineurin and mTOR inhibitors have opposing effects on regulatory T cells while reducing regulatory B cell populations in kidney transplant recipients.

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• dc.contributor.author Latorre, Ireneca
• dc.contributor.author Esteve-Solé, Anaca
• dc.contributor.author Redondo Pachón, María Doloresca
• dc.contributor.author Giest, Sandraca
• dc.contributor.author Argilaguet Marqués, Jordi, 1977-ca
• dc.contributor.author Álvarez, Saraca
• dc.contributor.author Peligero Cruz, Cristina, 1986-ca
• dc.contributor.author Forstmann, Isabelleca
• dc.contributor.author Crespo Barrio, Martaca
• dc.contributor.author Pascual Santos, Julioca
• dc.contributor.author Meyerhans, Andreasca
• dc.date.accessioned 2016-05-10T10:40:35Z
• dc.date.issued 2016
• dc.description.abstract BACKGROUND: Regulatory B (Breg) and T (Treg) cells represent a biomarker for tolerance in transplant patients. Despite the importance of Treg and Breg in transplantation and the suggested crosstalk between both suppressive cell populations, little is known on how they are influenced by long-term immunosuppressive treatment. The aim of the present study was to investigate the effect of different immunosuppressive drugs used in routine clinical practice on Treg and Breg cell numbers. METHODS: Thirty-six kidney transplant recipients with stable graft function were recruited and classified according to their concomitant therapy: 22 patients received calcineurin inhibitors (CNI) and 14 patients received mammalian target of rapamycin (mTOR) inhibitors. A group of 8 healthy untreated subjects was included as control. Absolute numbers of peripheral blood-derived IL10-producing B cells (CD19(+)IL10(+)), CD19(+)CD24(hi)CD38(hi) transitional B cells and Treg cells (CD4(+)CD25(+)FOXP3(+)) were quantified in all KT patients and controls by flow cytometry. RESULTS: CD19(+)CD24(hi)CD38(hi) transitional B cells increased over time and seem to be related with long-term therapeutic graft survival irrespective of the treatment regimen. CNI and mTOR inhibitors significantly reduced numbers of Breg cells when compared with healthy individuals, whereas mTOR inhibitors expanded Treg cells in comparison with CNI drugs. CONCLUSIONS: Bridging the drug-mediated reduction of Breg cell numbers in vivo with the requirements of Breg cells for long-term transplant success remains an as yet unresolved task for therapeutic intervention. Further larger cohort studies that evaluate the effect of different treatment regimen on defined lymphocyte subpopulations are warranted.ca
• dc.description.sponsorship DR and MC were supported by a grant Marató TV3 137/C/2012. JP was supported by grants/nFIS-ISCIII-FEDER PI13/00598 and RedinRenRD12/0021/0024. AM was supported by a Ministerio de Economía y Competitividad grant SAF2010–21336.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Latorre I, Esteve-Sole A, Redondo D, Giest S, Argilaguet J, Alvarez S. et al. Calcineurin and mTOR inhibitors have opposing effects on regulatory T cells while reducing regulatory B cell populations in kidney transplant recipients. Transpl Immunol. 2016 Mar;35:1-6. DOI: 10.1016/j.trim.2016.01.004ca
• dc.identifier.doi http://dx.doi.org/10.1016/j.trim.2016.01.004
• dc.identifier.issn 0966-3274
• dc.identifier.uri http://hdl.handle.net/10230/26261
• dc.language.iso engca
• dc.publisher Elsevierca
• dc.relation.ispartof Transplant Immunology. 2016 Mar;35:1-6
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-21336
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.trim.2016.01.004ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Medicaments immunosupressorsca
• dc.subject.other Cèl·lules Bca
• dc.subject.other Cèl·lules Tca
• dc.subject.other Ronyons -- Trasplantacióca
• dc.title Calcineurin and mTOR inhibitors have opposing effects on regulatory T cells while reducing regulatory B cell populations in kidney transplant recipients.ca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca