Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation

One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (T REG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect T REG proliferation. Purifi...

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Autores principales: Pino-Lagos,Karina, Michea,Paula, Sauma,Daniela, Alba,Andrea, Morales,Jorge, Bono,María Rosa, Fierro,Alberto, Rosemblatt,Mario
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2010
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602010000300010
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spelling oai:scielo:S0716-976020100003000102010-11-30Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferationPino-Lagos,KarinaMichea,PaulaSauma,DanielaAlba,AndreaMorales,JorgeBono,María RosaFierro,AlbertoRosemblatt,Mario CD4+CD25+ regulatory T cell Cyclosporine A dendritic cells transplant tolerance One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (T REG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect T REG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled T REG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of T REG cells from 72 to 47%. Further inhibition to a 24% of T REG proliferation was obtained as a direct effect of CsA on T REG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.43 n.3 20102010-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602010000300010en10.4067/S0716-97602010000300010
institution Scielo Chile
collection Scielo Chile
language English
topic CD4+CD25+ regulatory T cell
Cyclosporine A
dendritic cells
transplant tolerance
spellingShingle CD4+CD25+ regulatory T cell
Cyclosporine A
dendritic cells
transplant tolerance
Pino-Lagos,Karina
Michea,Paula
Sauma,Daniela
Alba,Andrea
Morales,Jorge
Bono,María Rosa
Fierro,Alberto
Rosemblatt,Mario
Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
description One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (T REG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect T REG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled T REG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of T REG cells from 72 to 47%. Further inhibition to a 24% of T REG proliferation was obtained as a direct effect of CsA on T REG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.
author Pino-Lagos,Karina
Michea,Paula
Sauma,Daniela
Alba,Andrea
Morales,Jorge
Bono,María Rosa
Fierro,Alberto
Rosemblatt,Mario
author_facet Pino-Lagos,Karina
Michea,Paula
Sauma,Daniela
Alba,Andrea
Morales,Jorge
Bono,María Rosa
Fierro,Alberto
Rosemblatt,Mario
author_sort Pino-Lagos,Karina
title Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
title_short Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
title_full Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
title_fullStr Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
title_full_unstemmed Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
title_sort cyclosporin a-treated dendritic cells may affect the outcome of organ transplantation by decreasing cd4+cd25+ regulatory t cell proliferation
publisher Sociedad de Biología de Chile
publishDate 2010
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602010000300010
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