IMPAIRED NEGATIVE SELECTION OF T-CELLS IN HODGKINS-DISEASE ANTIGEN CD30-DEFICIENT MICE

CD30 is found on Reed-Sternberg cells of Hodgkin's disease and on a va riety of non-Hodgkin's lymphoma cells and is up-regulated on cells aft er Epstein-Barr virus, human T cell leukemia virus, and HIV infections . We report here that the thymus in CD30-deficient mice contains eleva ted numbers of thymocytes. Activation-induced death of thymocytes afte r CD3 cross-linking is impaired both in vitro and in vivo. Breeding th e CD30 mutation separately into alpha beta TCR- or gamma delta TCR-tra nsgenic mice revealed a gross defect in negative but not positive sele ction. Thus, like TNF-receptors and Fas/Apo-1, the CD30 receptor is in volved in cell death signaling. It is also an important coreceptor tha t participates in thymic deletion.