Apoptosis of thymocytes during acute graft-versus-host disease is independent of glucocorticoids

Background Elimination of immature thymocytes resulting in thymic atrophy i s characteristic of acute graft-versus-host disease (aGVHD), Because aGVHD has been associated with elevated glucocorticoid (GC) production, and CD4,C D8 double-positive thymocytes undergo rapid apoptosis in response to GCs, w e hypothesized that administration of the GC receptor antagonist RU486 (mif epristone) should alter aGVHD-mediated thymocyte apoptosis, Methods. Thymic development in the presence of aGVHD was studied in a haplo identical nonirradiated murine transplantation model (C57BL/6-->B6D2F(1)). Recipients were treated with RU486 or vehicle done. Thymic development was analyzed by flow cytometry at different times post transplant. Results, Acute thymic GVHD was characterized (1) by infiltration of mature donor-derived T cells and (2) by increased apoptosis of immature CD4(+) CD8 (+) thymocytes between 1 and 2 weeks after allogeneic transplantation. Cont rary to expectations, administration of RU486 had no effect on these two pa rameters. Conclusions. Our data suggest that thymic pathology during aGVRD is mediate d via a glucocorticoid-independent mechanism of apoptosis as blockade of gl ucocorticoid receptors did not alter the GVHD-induced thymic phenotype.