This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Approximately 15,000 allogeneic hematopoietic stem cell transplants (HSCT) were performed world-wide in 2000. In the treatment of cancer, these transplants offer beneficial allogeneic graft-vs.-tumor effects in which the transplanted cells attack the patients cancer cells. However these transplanted cells can also attack the other tissues in the patient resulting in a disease process known as graft-vs.-host disease (GVHD). GVHD remains a significant cause of illness following allogeneic HSCT. Cells produce a number of small molecules known as cytokines that allow them to communicate and direct other cells in the body. The overall goal of this project is to determine if the cytokines IL-12 and/or IL-23 are potential targets for therapeutic manipulation to promote the anti-cancer activity of allogeneic HSCT s while reducing the incidence or severity of GVHD. The hypothesis is that the cytokine IL-12 will help direct and sustain the attack of the transplanted cells to the cancer. It is predicted that IL-23 will be more important in promoting the attack of the transplanted cells against the recipients own tissues. Furthermore, IL-12 will help reduce the severity of the tissue damage caused by IL-23. This project uses two different strains of mice that will result in GVHD when hematopoietic cells are transplanted from one mouse into the other. These mice are available as wild type (can make both IL-12 and IL-23), IL-12 and IL-23 deficient or IL-12 deficient animals and allow us to characterize and measure the disease process when these cytokines are present or absent in the cells of the mouse that is donating the cells or the animal that is receiving the cells. In some experiments the recipient mouse is given tumor cells before the transplant so that the ability of the transplanted cells to attack the cancer can be measured when the animals lack these cytokines.
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