In this project, we hypothesize that stem cell isolates from donors with immunologic disease may be engrafted into SCID mice, providing a model to study the induction, pathogenesis, and regulation of human immunologic disease """"""""in vivo in the mouse."""""""" The initial immunologic disease we will pursue will be ragweed allergic asthma. This disease has a high prevalence, and the inciting antigen is very well characterized.
Our specific aims for this project are: 1. To characterize the optimal conditions for human stem cell engraftment into SCID-Hu mice. Parameters to be studied include stem cell source (bone marrow vs. peripheral blood), requirements for accessory cells and stromal elements, optimal conditioning regimens for the recipients, and dose-response and kinetic parameters. 2. To use SCID-Hu mice engrafted with BMPC or PBPC isolates from human atopic donors to investigate: a) the dose-response, kinetics, and conditions necessary for the development of allergen-specific immune responses, and b) the regulation of these responses by a variety of small molecular entities and biologics.
