Project description:Lethally irradiated C57Bl/6 Act-mOVA mice receiving allogeneic hematopoietic stem cell transplantation (aHSCT) from C57Bl/6 OT-I animals develop acute graft versus host disease (aGvHD) in a CD8+ T cell-dependent, reproducible manner, and succumb to the disease within 4-7 days. Tracking of UBC-GFP/OT-I graft CD8+ T cells discloses heavy infiltration of the GI tract, liver and lungs at the onset of the disease, and hallmark histologic features of acute gastrointestinal and hepatic GvHD, and aGVHD-associated lymphocytic bronchitis. This dataset describes gene expression patterns of CD45.1/OT-1 CD8+ T cells retrieved from the graft before (aHSCT + Day 0), and from various target organs of the host after (aHSCT + Day 4) grafting them into Act-mOVA recipients.
Project description:This study seeks a better understanding of the functional differences emerging between mouse CD8+ T effector (Teff) cells infiltrating three distinct mucosal environments; the small intestine, the lung and the liver. CD8+ Teff cells immigrating in the target organs were generated using a murine experimental acute graft versus host disease (aGVHD) model. For this purpose, congenially labeled CD45.1 OT-I CD8+ Teff cells were transplanted to and activated in a lethally irradiated allogeneic CD45.2 host constitutively expressing their cognate antigen, the chicken ovalbumin protein. CD8+ Teff cells were retrieved from their respective organ environments by automated organ disintegration and MACS sorting, and compared with each other by whole genome gene expression profiling. Peripheral blood derived circulating CD8+ Teff cells were also analyzed, serving as circulating peripheral T effector cell controls
Project description:Acute GVHD is known to damage the structure of peripheral lymphoid organs. This study investigates how peripheral tolerance induction is affected by lymph node stroma damage in the context of graft-versus-host disease. Fibroblastic reticular cells (FRC) were flow sorted on day 7 post allo-BMT in mice developing acute GVHD, transplanted no GVHD-recipients or untransplanted control mice. The single miHA-mismatch female into male transplantation model was used (acute GVHD group: T-cell depleted bone marrow (TCDBM) + HY-specific TCR-transgenic MataHari CD8+ T cells into C57BL/6 male recipients; no GVHD group: TCDBM only).
Project description:The effect of tauroursodeoxycholic acid on the development of acute graft-versus-host disease was tested in a murine allogeneic stem cell transplantation model. TUDCA was shown to reduce acute GVHD by reducing intestinal antigen presentation and following apoptosis and increasing the viability of intestinal epithelial cells.
Project description:The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation. Recently, an activating effect of rapamycin on the function of myeloid-derived suppressor cells (MDSCs), a subset of immune suppressive cells of myeloid origin was reported. However, the effect of rapamycin treatment on MDSCs induction and function in the management of graft-versus-host disease is largely unknown. We used an MHC class I and II mismatched parent into F1 bone marrow transplantation mouse model to elucidate the mechanisms of rapamycin on MDSCs in the context of graft-versus-host disease prevention. To define the impact of rapamycin therapy on MDSCs gene expression profile, we performed mircoarray analysis and compared gene expression profiles of ex vivo isolated MDSCs from rapamycin and PBS treated mice
Project description:The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation We used an MHC class I and II mismatched parent into F1 bone marrow transplantation mouse model to elucidate the mechanisms of rapamycin on T cells in the context of graft-versus-host disease prevention. To define the impact of rapamycin therapy on T cells gene expression profile, we performed mircoarray analysis and compared gene expression profiles of sorted splenic T cells from rapamycin and PBS treated mice
Project description:RATIONALE: Beclomethasone may be an effective treatment for graft-versus-host disease.
PURPOSE: Phase I/II trial to study the effectiveness of beclomethasone in treating patients who have graft-versus-host disease of the esophagus, stomach, small intestine, or colon.
