Dogs are a valuable preclinical PD0325901 model for transplantation studies, including adoptive immunotherapy with donor lymphocytes. Conversion of mixed-haematological-chimerism into complete-donor-chimerism thereby simulate efficacy of transplantation [21, 72, 73]. In conclusion, after establishing the implements for the generation of cUTY-specific CTLs, we are able to use this mixed-chimerism model as an in vivo model for the treatment of leukemic relapse with UTY-specific CTLs.
In up to 50% of the females we could induce a UTY-specific reaction (W248) in male-DLA-identical animals in vitro and in vivo. This is a very promising starting point for exploitation of our preclinical canine-model for leukemia treatment in humans: Ex vivo-generated UTY-specific-female-donor CTLs using UTY-derived-peptide-loaded DCs will be transfused to male-recipients in the course of DLT after transplantation in order to prevent or cure AML-relapse. We thank the people from the animal facility (Helmholtz Center Munich), especially M. Hagemann, S. Schlink and V. Terkowski for taking care of the dogs. We also thank I. Laaser and J. Adamski (Helmholtz Center Munich, Neuherberg) for providing the canine-UTY-mRNA sequence. Supports: DLR-grant 01GU0516 (D. Bund); Deutsche-José-Carreras-Stiftung-e.V. (H.J. Kolb). All authors concur with the manuscript
submission and have no financial/commercial conflict of interest to disclose. “
“The dendritic cell (DC) lineage is remarkably heterogeneous. selleck kinase inhibitor It has been postulated that specialized DC subsets have evolved in order to select and support selleck chemical the multitude of possible T cell differentiation pathways. However, defining the function of individual
DC subsets has proven remarkably difficult, and DC subset control of key T cell fates such as tolerance, T helper cell commitment and regulatory T cell induction is still not well understood. While the difficulty in assigning unique functions to particular DC subsets may be due to sharing of functions, it may also reflect a lack of appropriate physiological in-vivo models for studying DC function. In this paper we review the limitations associated with many of the current DC models and highlight some of the underlying difficulties involved in studying the function of murine DC subsets. Dendritic cells (DCs) are professional antigen-presenting cells critically required for the initiation of T cell responses. Some DC subsets sample antigens in peripheral tissues and transport them to the lymph node (LN), where DCs come into contact with recirculating naive T cells. Other DC subsets are strategically positioned within secondary lymphoid organs to capture blood-borne antigens and present them to T cells (reviewed in [1]).