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Biological Research

versão impressa ISSN 0716-9760

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PINO-LAGOS, Karina et al. Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation. Biol. Res. [online]. 2010, vol.43, n.3, pp.333-337. ISSN 0716-9760.  http://dx.doi.org/10.4067/S0716-97602010000300010.

One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (TREG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect TREG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled TREG 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 TREG cells from 72 to 47%. Further inhibition to a 24% of TREG proliferation was obtained as a direct effect of CsA on TREG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.

Palavras-chave : CD4+CD25+ regulatory T cell; Cyclosporine A; dendritic cells; transplant tolerance.

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