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

• Karina Pino-Lagos ^[1] ; Paula Michea ^[1] ; Daniela Sauma ^[1] ; Andrea Alba ^[2] ; Jorge Morales ^[2] ; María Rosa Bono ^[1] ; Alberto Fierro ^[2] ; Mario Rosemblatt ^[1]
  1. [1] Universidad de Chile

     Universidad de Chile

     Santiago, Chile

     
  2. [2] Clínica Las Condes

     Clínica Las Condes

     Santiago, Chile

     
• Localización: Biological Research, ISSN-e 0717-6287, ISSN 0716-9760, Vol. 43, Nº. 3, 2010, págs. 333-337
• Idioma: inglés
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• Resumen

  • 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.