Cyclosporin a-treated dendritic cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory t cell proliferation

Karina Pino-Lagos, Paula Michea, Daniela Sauma, Andrea Alba, Jorge Morales, María Rosa Bono, Alberto Fierro, Mario Rosemblatt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)333-337
Number of pages5
JournalBiological Research
Volume43
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Cyclosporine a
  • Dendritic cells
  • Transplant tolerance

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