Flt3L-mobilized dendritic cells bearing H2-Kbm1 apoptotic cells do not induce cross-tolerance to CD8+ T cells across a class I MHC mismatched barrier

[EN] Tolerization of allogeneic CD8+ T cells is still a pending issue in the field of transplantation research to achieve long-term survival. To test whether dendritic cells (DC) bearing allogeneic major histocompatibility complex (MHC) class I mismatched apoptotic cells could induce cross-tolerance...

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Detalles Bibliográficos
Autores: Río González, María Luisa del, Cote Sierra, Javier, Rodríguez Barbosa, José Ignacio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/19925
Acceso en línea:https://onlinelibrary.wiley.com/doi/10.1111/j.1432-2277.2011.01220.x
https://hdl.handle.net/10612/19925
Access Level:acceso abierto
Palabra clave:Inmunología
Apoptotic cells
CD103
Cross-tolerance
Dendritic cell
Flt3L
Transplantation
3109.03 Inmunología
Descripción
Sumario:[EN] Tolerization of allogeneic CD8+ T cells is still a pending issue in the field of transplantation research to achieve long-term survival. To test whether dendritic cells (DC) bearing allogeneic major histocompatibility complex (MHC) class I mismatched apoptotic cells could induce cross-tolerance to alloreactive CD8+ T cells, the following experimental strategy was devised. Rag2/γc KO B6 mice were treated with Fms-like tyrosine kinase 3 ligand (Flt3L)-transduced B16 melanoma cells to drive a rapid expansion and mobilization of DC in vivo. Of all DC populations expanded, splenic CD11c+CD103+CD8α+ DC were selectively involved in the process of antigen clearance of X-ray irradiated apoptotic thymocytes in vivo. Considering that CD11c+CD103 +CD8α+ DC selectively take up apoptotic cells and that they are highly specialized in crosspresenting antigen to CD8+ T cells, we investigated whether B6 mice adoptively transferred with Flt3L-derived DC loaded with donor-derived apoptotic thymocytes could induce tolerance to bm1 skin allografts. Our findings on host anti-donor alloresponse, as revealed by skin allograft survival and cytotoxic T lymphocyte assays, indicated that the administration of syngeneic DC presenting Kbm1 donor-derived allopeptides through the indirect pathway of antigen presentation was not sufficient to induce cross-tolerance to alloreactive CD8+ T cells responding to bm1 alloantigens in a murine model of skin allograft transplantation across an MHC class I mismatched barrier