TUMOR-NECROSIS-FACTOR RECEPTOR P55 MEDIATES DELETION OF PERIPHERAL CYTOTOXIC T-LYMPHOCYTES IN-VIVO

Cellular death of activated lymphocytes down-regulates immune response s and is involved in maintaining self tolerance. Signals associated wi th ligation of the membrane molecule Fas lead to lymphocyte apoptosis, but additional, Fas-independent mechanisms have been postulated. Here , we show a marked expansion and prolonged persistence of functional a ctivated cytotoxic T cells in mice lacking the tumor necrosis factor ( TNF) receptor p55. In the absence of this receptor, peripheral lymphoc yte apoptosis was significantly reduced in vivo. The prolonged thymocy te survival was associated with functional anergy, since the T cells n o longer proliferated in vitro when stimulated with peptide antigen. H owever, specific cytotoxic effector function was easily detected in vi tro. We conclude that the TNF receptor p55 is involved in peripheral T cell deletion in vivo.