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BACKGROUND: Elimination of immature thymocytes resulting in thymic atrophy is characteristic of acute graft-versus-host disease (aGVHD). Because aGVHD has been associated with elevated glucocorticoid (GC) production, and CD4,CD8 double-positive thymocytes undergo rapid apoptosis in response to GCs, we hypothesized that administration of the GC receptor antagonist RU486 (mifepristone) should alter aGVHD-mediated thymocyte apoptosis. METHODS: Thymic development in the presence of aGVHD was studied in a haploidentical nonirradiated murine transplantation model (C57BL/6-->B6D2F1). Recipients were treated with RU486 or vehicle alone. 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. Contrary to expectations, administration of RU486 had no effect on these two parameters. CONCLUSIONS: Our data suggest that thymic pathology during aGVHD is mediated via a glucocorticoid-independent mechanism of apoptosis as blockade of glucocorticoid receptors did not alter the GVHD-induced thymic phenotype.

Type

Journal article

Journal

Transplantation

Publication Date

27/05/2000

Volume

69

Pages

2190 - 2193

Keywords

Animals, Apoptosis, Atrophy, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Flow Cytometry, Graft vs Host Disease, Lymphocyte Transfusion, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mifepristone, Receptors, Glucocorticoid, T-Lymphocytes, Thymus Gland, Transplantation, Homologous, Transplantation, Isogeneic