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* Department of Pathology and Committee in Immunology, University of Chicago, Chicago, IL 60637;
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;
University of Helsinki and National Public Health Institute, Helsinki, Finland; and
Department of Immunology, Baylor College of Medicine, Houston, TX 77030
Ectopic expression of peripherally restricted Ags by medullary thymic epithelial cells (mTECs) is associated with negative selection. Autoimmune regulator (AIRE) is considered to be the master regulator of these Ags. We show in this study that the ectopic expression of type II collagen (CII) in mTECs and the corresponding central tolerance to CII are AIRE independent but lymphotoxin dependent. The failure to properly express CII in mTECs of Lta–/– and Ltbr–/– mice leads to overt autoimmunity to CII and exquisite susceptibility to arthritis. These findings define the existence of additional pathways of ectopic peripheral Ag expression, parallel to and independent of AIRE, which may cover an extended spectrum of peripheral Ags in the thymus.
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