Induction of mixed vs full chimerism to potentiate GVL effects after bone-marrow transplantation.
Graft-vs-host (GVH) alloresponses mediated by delayed donor lymphocyte infusions (DLI) can occur in the absence of GVHD (graft-vs-host disease). These GVH responses are confined to the lymphohematopoietic system and mediate graft-vs-leukemia (GVL) reactions without causing GVHD. Although interaction of donor T-cells with host-derived antigen-presenting cells (APC) is central to the development of GVHD, we were able to show that this T-cell/APC interaction is also critical for the induction of GVL, which can occur in the absence of GVHD if donor T-cell administration is delayed to a time point after bone-marrow transplant (BMT) when conditioning-induced inflammation has subsided. Induction of mixed hematopoietic chimerism using the method described below allows analysis of these interactions between host APC and donor T-cells.
Mapara
Markus Y
MY
Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Sykes
Megan
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D045744:Cell Line, Tumor; D002678:Chimera / Q000276:immunology*; D046528:Chimerism; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors