Open AccessFlt3L‐mobilized dendritic cells bearing H2‐K bm1 apoptotic cells do not induce cross‐tolerance to CD8 + T cells across a class I MHC mismatched barrier
Author(s) -
del Rio MariaLuisa,
CoteSierra Javier,
RodriguezBarbosa JoseIgnacio
Publication year - 2011
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2011.01220.x
Subject(s) - cytotoxic t cell , cd8 , cd11c , immunology , antigen , mhc class i , major histocompatibility complex , cross presentation , antigen presenting cell , cancer research , medicine , microbiology and biotechnology , t cell , biology , immune system , in vitro , biochemistry , phenotype , gene
Summary 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.