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

• Main Authors: Karina Pino-Lagos, Paula Michea, Daniela Sauma, Andrea Alba, Jorge Morales, María Rosa Bono, Alberto Fierro, Mario Rosemblatt
• Format: Article
• Language: English
• Published: BMC 2010-01-01
• Series: Biological Research
• Subjects: CD4+CD25+ regulatory T cell; Cyclosporine A; dendritic cells; transplant tolerance
• Online Access: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602010000300010

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.