MRL-lpr/lpr disease: theories meet Fas.
It has been exciting for scientists to postulate all sorts of derangements to explain the numerous observations regarding the disease of MRL-lpr/lpr mice. Until recently, our imaginations have had almost free reign, unconstrained by any true knowledge. Now, however, it has been found that the lpr gene represents a mutation which causes a defect in a cell surface molecule, Fas. Since the normal Fas is thought to be important in programmed cell death, apoptosis, the lpr-associated defect in Fas is thought to interfere with normal apoptosis. Therefore, we are forced to reconsider all hypotheses regarding lpr/lpr mice in terms of a defect in Fas. This paper represents such an attempt. It suggests that failure of peripheral apoptosis of CD4+ cells allows self-reactive helper T cells to persist and drive autoantibody production. Failure of apoptosis of self-reactive CD8+ cells leads to down-regulation of CD8 and persistence as CD4-, CD8- T cells which contribute to the lymphadenopathy.
Steinberg
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MITRE Corporation, McLean, VA 22102.
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D001323:Autoantibodies / Q000096:biosynthesis*; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D019014:fas Receptor
D000954:Antigens, Surface; D001323:Autoantibodies; D019014:fas Receptor