Perforin protects against autoimmunity in lupus-prone mice.
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- alphabeta 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.
Peng
S L
SL
Department of Biology, Yale University, New Haven, CT 06510, USA.
Moslehi
J
J
Robert
M E
ME
Craft
J
J
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016019:Survival Analysis; D019014:fas Receptor / Q000235:genetics
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin