The goals of this Project are to enhance our understanding of graft vs host disease (GVHD) andgraft vs tumor (GVT) reactions to gain greater insight into these complex biological reactions and to developstrategies which may be translated to the clinic. We will utilize a novel bioluminescent imaging strategywhereby cell populations of interest are labeled with the luciferase (luc) gene and emit light. Towards thisend we have generated a unique gfp/luc transgenic mouse line to ensure uniform gene expression andavailability of labeled cell populations. Trafficking and survival of luc* cells can be followed in real time withhigh precision and sensitivity. We will evaluate the GVHD inducing capacity of primary CD4+ and CDS* Tcells with respect to the location of key events in GVHD induction. We hypothesize that GVHD developsthrough the spatial and temporal migration of lymphocytes to key sites whereby alloreactive cells proliferateand upregulate other cell surface molecules required for entry into GVHD target organs such as thegastrointestinal tract, skin and liver. Bioluminescent based imaging will be utilized to identify the major sitesof GVHD induction to direct tissue sampling and characterization of the infiltrating cell populations by FACSand immunofluorescence. We will further explore cell populations known to have GVT reactivity yet withlimited GVHD potential to compare and contrast the trafficking and survival characteristics of these cells toprimary T cells. We will focus on the use of cytokine induced killer (CIK) and natural killer (NK) cells sinceboth cell populations have been shown to not result in clinically significant GVHD in clinical trials and maypromote GVT effects. This basic and translational project will provide insights into GVHD pathophysiologyand characterize cell populations capable of GVHD and GVT effects that could be translated to the clinicwhere CIK cells are being explored in Project 1, This Project interacts with Projects 1,2,4,5,7 and 8 andutilizes all of the Cores.
Showing the most recent 10 out of 307 publications
