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.

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.
(© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)