title: Depletion of complement does not impact initiation of xenobiotic-induced autoimmune disease.
abstract: Deficiency in Daf1, a complement regulatory protein, has been shown to exacerbate development of various autoimmune diseases and recent studies have suggested that this may be explained by Daf1 acting to limit T-cell hyper-responsiveness. It has been suggested that the absence of Daf1 aggravates autoimmune disease in a complement-dependent manner, but others have shown that activation of T cells in the absence of Daf1 can be complement independent. However, the relationship between Daf1, complement components, lymphocyte activation, cytokine expression and antibody production remains to be determined in mice that are not Daf1 deficient. We have recently demonstrated, in murine mercury-induced autoimmunity (mHgIA), that an accumulation of CD44(high) Daf(low) CD4(+) T cells is associated with the development of autoimmunity. In this study we observed that complement depletion does not affect the accumulation of activated CD4(+) T cells, elevation of splenic interleukin-4 expression and autoantibody production in mHgIA. In addition, neither the accumulation of CD44(high) Daf(low) CD4(+) T cells nor the down-regulation of Daf1 expression on CD4(+) T cells was influenced by a lack of complement. In conclusion, these studies show that initiating events in xenobiotic-induced autoimmunity, including lymphocyte activation, cytokine expression and autoantibody production, are not dependent on complement.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Cauvi
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Toomey
authors.forename: K Michael
authors.initials: KM
authors.lastname: Pollard
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018958:CD55 Antigens / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D003165:Complement System Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015262:Xenobiotics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D018958:CD55 Antigens; D003176:Complement C3; D051056:Complement Inactivating Agents; D016207:Cytokines; D004546:Elapid Venoms; D015262:Xenobiotics; C016310:cobra venom factor; C521184:decay-accelerating factor 1, mouse; D008627:Mercuric Chloride; D003165:Complement System Proteins