Effects of hemizygous CD45 expression in the autoimmune Faslgld/gld syndrome

Mice homozygous for the Fasl(gld/gld) mutation cannot initiate apoptosis via the Fas/Fasl pathway and develop an autoimmune disease characterized by the accumulation of CD4(-)/CD8(-) (DN) T cells and a progressive T cell anergy. These DN T cells express a high-molecular-weight isoform of the membrane PTPase CD45 (B220). We have produced a Fasl(gld/gld) mouse strain with only one functional CD45 allele (CD45(+/-), Fasl(gld/gld)) in order to explore the role that CD45 plays in the lymphoaccumulation and proliferative capacity of the DN T cells. In contrast to CD45(+/+), Fasl(gld/gld) mice, CD45(+/-), Fasl(gld/gld) mice display a 10-fold reduction in the DN T cell population and have decreased levels of anti-DNA antibodies and total serum Ig. However, enriched DN T cell populations remain unresponsive to mitogenic stimulation, but do display altered patterns of tyrosine phosphorylation. These data indicate that CD45 is essential to the accumulation of DN T cells in Fasl(gld/gld) mice and implicate CD45 as a component of the process of deletion that normally governs the composition of the T cell population. (C) 2001 Academic Press.