GLD GLD MICE ARE UNABLE TO EXPRESS A FUNCTIONAL LIGAND FOR FAS/

Mice homozygous for either the lpr or gld genes develop phenotypically identical autoimmune disorders. The gene responsible for the patholog y in lpr/lpr mice encodes the Fas antigen, a protein associated with t he induction of programmed cell death. To determine if the defect asso ciated with gld represents a mutation in the ligand for Fas, we have a ssessed the ability of lymphoid cells from homozygous gld/gld mice to lyse target cells in a Fas-dependent manner. Using an antagonistic ant ibody to Fas, we demonstrate that activated T cells from normal and lp r mice are capable of inducing Fas-mediated lysis of tumor target cell s. In contrast, activated T cells from gld/gld mice fail to induce lys is of tumor targets, although cells from gld mice are able to lyse spe cific allogeneic targets following mixed lymphocyte culture. In additi on, activated T cells from gld/gld homozygous animals are not capable of binding to a Fas. Fc fusion protein at high levels, whereas activat ed T cells from normal and lpr/lpr animals bind Fas. Fc efficiently. T hese data indicate that mice homozygous for gld are unable to express a functional ligand for Fas.