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 (HEL) were crossed with mice expressing HEL on the thyroid epithelium, on pancreatic islet β cells, or systemically. Depending on the pattern of HEL expression, deletion of double-positive thymocytes ranged from minimal to complete,...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1997-08, Vol.7 (2), p.255-271
Main Authors: Akkaraju, Srinivas, Ho, William Y, Leong, Denise, Canaan, Karen, Davis, Mark M, Goodnow, Christopher C
Format: Article
Language:English
Subjects:
Animals
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - enzymology
CD4-Positive T-Lymphocytes - immunology
Cell Movement - genetics
Cell Movement - immunology
Chickens
Enzyme Activation - genetics
Enzyme Activation - immunology
Epitopes, T-Lymphocyte - genetics
Epitopes, T-Lymphocyte - immunology
Immune Tolerance - genetics
Immunophenotyping
Inflammation - etiology
Inflammation - immunology
Inflammation - pathology
Islets of Langerhans - immunology
Islets of Langerhans - metabolism
Islets of Langerhans - pathology
Lymphocyte Count
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Muramidase - antagonists & inhibitors
Muramidase - biosynthesis
Muramidase - immunology
Necrosis
Organ Specificity - genetics
Organ Specificity - immunology
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Antigen, T-Cell, alpha-beta - immunology
Thyroid Gland - enzymology
Thyroid Gland - immunology
Thyroid Gland - pathology
Thyroiditis, Autoimmune - etiology
Thyroiditis, Autoimmune - immunology
Thyroiditis, Autoimmune - pathology
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Summary:T cell receptor (TCR) transgenic mice specific for hen egg lysozyme (HEL) were crossed with mice expressing HEL on the thyroid epithelium, on pancreatic islet β cells, or systemically. Depending on the pattern of HEL expression, deletion of double-positive thymocytes ranged from minimal to complete, and peripheral CD4 cells exhibited graded reduction in TCR expression, in vitro responsiveness, and in vivo helper ability. CD4 cells were least tolerant in TCR/thyroid-HEL and TCR/islet-HEL mice, which developed an extensive lymphocytic thyroiditis or insulitis that nevertheless did not eliminate HEL-expressing endocrine cells. Autoreactive CD4 clones thus escape the thymus under a range of circumstances, retain sufficient function to initiate subclinical autoimmune inflammation when self-antigens are concentrated in the thyroid or pancreas, and may regulate progression of subclinical inflammation to destructive autoimmune disease.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80528-2