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. 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.
Laboratorio de Inmunología, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
Karina
K
Pino-Lagos
Paula
P
Michea
Daniela
D
Sauma
Andrea
A
Alba
Jorge
J
Morales
María Rosa
MR
Bono
Alberto
A
Fierro
Mario
M
Rosemblatt
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016377:Organ Transplantation; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D007166:Immunosuppressive Agents; D007378:Interleukins; D016572:Cyclosporine