A specific intercellular pathway of apoptotic cell death is defective in the mature peripheral T cells of autoimmunelprandgldmice

摘要

AbstractHomozygosity for either of the unlinked murine autosomal recessive mutationslprorgldleads to autoimmunity characterized by peripheral accumulation of CD4−/CD8−“double‐negative” T cells, autoantibodies and various forms of tissue pathology. Recently, the gene affected bylprwas identified asfas, whose product acts as a trigger for programmed cell death or apoptosis. Data reported here indicate that the Fas receptor and its ligand, the wild‐type form of thegldgene product, are essential for antigen‐stimulated peripheral T cell apoptosis. Furthermore, the wild‐typegldgene product is a non‐cell‐autonomous protein that is produced by activated T cells. Apoptotic elimination of antigen‐receptor‐triggered peripheral T cells appears to be abnormal inlprandgldmice, and this deficiency causes peripheral T cells to accumulate resulting in lymphadenopathy. These findings support the importance of apoptotic regulation of lymphocyte persistence after a