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*
Section of Rheumatology and
Department of Pathology, Yale University School of Medicine, and
Department of Biology, Yale University, New Haven, CT 06510
The roles of cytolytic regulatory mechanisms in the immune system
of lupus-prone mice were examined in perforin-deficient animals bearing
functional or defective (lpr) Fas Ag (CD95).
Perforin-deficient Fas+ animals developed accelerated
autoimmunity, characterized by increased hypergammaglobulinemia,
autoantibody production, and immune deposit-related end-organ disease
compared with perforin-intact counterparts. In comparison,
perforin-deficient lpr animals had accelerated mortality
compared with perforin-intact lpr mice, associated with the
abnormal accumulation of CD3+CD4-CD8- 
ß
T cells in conjunction with unaltered hypergammaglobulinemia,
autoantibody production, and immune complex renal disease. These
results indicate that cytolytic lymphoid regulation plays critical
roles in the immune homeostasis of lupus-prone animals, and identify
perforin-mediated cytotoxicity as a specific mechanism in the
regulation of systemic autoimmunity.
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