Cellular and Molecular Characterization of the scurfy Mouse Mutant

摘要: Mice hemizygous (Xsf/Y) for the X-linked mutation scurfy (sf) develop a severe and rapidly fatal lymphoproliferative disease mediated by CD4+CD8- T lymphocytes. We have undertaken phenotypic functional studies to more accurately identify immunologic pathway(s) affected this important mutation. Flow cytometric analyses of lymphoid cell populations reveal that syndrome is characterized changes in several parameters, including an increase Mac-1+ cells decrease B220+ cells, may result from production extremely high levels cytokine granulocyte-macrophage CSF cells. Scurfy also exhibit strong up-regulation surface Ags indicative vivo activation, CD69, CD25, CD80, CD86. Both normal are responsive two distinct signals provided TCR ligation CD28; however, hyperresponsive decreased requirement costimulation through CD28 relative controls. This hypersensitivity result, part, increased B7-1 B7-2, whose expression up-regulated on Although specific defect leading hyperactivation has not been identified, we demonstrate less sensitive than controls inhibitors tyrosine kinases such as genistein herbimycin A, immunosuppressant cyclosporin A. One interpretation our data would suggest results defect, which interferes with down-regulation activation.