A RANGE OF CD4 T-CELL TOLERANCE - PARTIAL INACTIVATION TO ORGAN-SPECIFIC ANTIGEN ALLOWS NONDESTRUCTIVE THYROIDITIS OR INSULITIS

T cell receptor (TCR) transgenic mice specific for hen egg lysozyme (H EL) were crossed with mice expressing HEL on the thyroid epithelium, o n pancreatic islet beta cells, or systemically. Depending on the patte rn of HEL expression, deletion of double-positive thymocytes ranged fr om minimal to complete, and peripheral CD4 cells exhibited graded redu ction in TCR expression, in vitro responsiveness, and in vivo helper a bility. CD4 cells were least tolerant in TCR/thyroid-HEL and TCR/islet -HEL mice, which developed an extensive lymphocytic thyroiditis or ins ulitis that nevertheless did not eliminate HEL-expressing endocrine ce lls. Autoreactive CD4 clones thus escape the thymus under a range of c ircumstances, retain sufficient function to initiate subclinical autoi mmune inflammation when self-antigens are concentrated in the thyroid or pancreas, and may regulate progression of subclinical inflammation to destructive autoimmune disease.