title: 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.
abstract: 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/γ(c) 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 cross-presenting 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 K(bm1) 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.
authors.affiliation: Immunobiology Section, Institute of Biomedicine, University of León, León, Spain.
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: del Rio
authors.forename: Javier
authors.initials: J
authors.lastname: Cote-Sierra
authors.forename: Jose-Ignacio
authors.initials: JI
authors.lastname: Rodriguez-Barbosa
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D039521:CD11c Antigen / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006650:Histocompatibility Testing; D007108:Immune Tolerance; D039001:Integrin alpha Chains / Q000096:biosynthesis; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D013950:Thymus Gland / Q000166:cytology; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D039521:CD11c Antigen; D015395:Histocompatibility Antigens Class I; D039001:Integrin alpha Chains; C091367:alpha E integrins; D051941:fms-Like Tyrosine Kinase 3