T Cell Tolerance to a Neo-Self Antigen Expressed by Thymic Epithelial Cells: The Soluble Form Is More Effective Than the Membrane-Bound Form
Copyright policy )T Cell Tolerance to a Neo-Self Antigen Expressed by Thymic Epithelial Cells: The Soluble Form Is More Effective Than the Membrane-Bound Form
Abstract We have previously shown that transgenic (Tg) mice expressing either soluble or membrane-bound hen egg lysozyme (sHEL or mHEL, respectively) under control of the αA-crystallin promoter develop tolerance due to thymic expression of minuscule amounts of HEL. To further address the mechanisms by which this tolerance develops, we mated these two lines of Tg mice with the 3A9 line of HEL-specific TCR Tg mice, to produce double-Tg mice. Both lines of double-Tg mice showed deletion of HEL-specific T cells, demonstrated by reduction in numbers of these cells in the thymus and periphery, as well as by reduced proliferative response to HEL in vitro. In addition, the actual deletional process in thymi of the double-Tg mice was visualized in situ by the TUNEL assay and measured by binding of Annexin V. Notably, the apoptosis localized mainly in the thymic medulla, in line with the finding that the populations showing deletion and increased Annexin V binding consisted mainly of single- and double-positive thymocytes. Interestingly, the thymic deletional effect of sHEL was superior to that of mHEL in contrast to the opposite differential tolerogenic effects of these HEL forms on B cells specific to this Ag. Analysis of bone marrow chimeras indicates that both forms of HEL are produced by irradiation-resistant thymic stromal cells and the data suggest that sHEL is more effective in deleting 3A9 T cells due mainly to its higher accessibility to cross-presentation by dendritic APC.
- National Institutes of Health United States
- National Cancer Institute United States
- Australian National University Australia
- National Institute of Health Pakistan
- National Eye Institute United States
dendritic cell, Dose-Response Relationship, Immunologic, Clonal Deletion, Apoptosis, Mice, Transgenic, Eye, Lymphocyte Activation, Autoantigens, lipocortin 5, animal tissue, Immunophenotyping, Mice, binding affinity, binding kinetics, In Situ Nick-End Labeling, Animals, controlled study, Antigens, Eye Proteins, lysozyme, cell population, Inflammation, immunolo, Antigen Presentation, gene deletion, animal model, flow cytometry, apoptosis, article, Membrane Proteins, Epithelial Cells, Mice, Inbred C57BL, Self Tolerance, eye inflammation, Keywords: alpha crystallin, antigen expression, Muramidase
dendritic cell, Dose-Response Relationship, Immunologic, Clonal Deletion, Apoptosis, Mice, Transgenic, Eye, Lymphocyte Activation, Autoantigens, lipocortin 5, animal tissue, Immunophenotyping, Mice, binding affinity, binding kinetics, In Situ Nick-End Labeling, Animals, controlled study, Antigens, Eye Proteins, lysozyme, cell population, Inflammation, immunolo, Antigen Presentation, gene deletion, animal model, flow cytometry, apoptosis, article, Membrane Proteins, Epithelial Cells, Mice, Inbred C57BL, Self Tolerance, eye inflammation, Keywords: alpha crystallin, antigen expression, Muramidase
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