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

Transpl Int. 2011 May;24(5):501-13. doi: 10.1111/j.1432-2277.2011.01220.x. Epub 2011 Jan 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Apoptosis
  • CD11c Antigen / biosynthesis
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Testing
  • Immune Tolerance
  • Integrin alpha Chains / biosynthesis
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Skin Transplantation
  • Thymus Gland / cytology
  • fms-Like Tyrosine Kinase 3 / metabolism*


  • Antigens, CD
  • CD11c Antigen
  • Histocompatibility Antigens Class I
  • Integrin alpha Chains
  • alpha E integrins
  • fms-Like Tyrosine Kinase 3