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  • 1
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    Projection of an immunological self shadow within the thymus by the aire protein (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-10-12
    Description: Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue- restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Mark S -- Venanzi, Emily S -- Klein, Ludger -- Chen, Zhibin -- Berzins, Stuart P -- Turley, Shannon J -- von Boehmer, Harald -- Bronson, Roderick -- Dierich, Andree -- Benoist, Christophe -- Mathis, Diane -- 2 P30 DK36836-16/DK/NIDDK NIH HHS/ -- 2T32 DK07260-26/DK/NIDDK NIH HHS/ -- KO8-DK59958-01A1/DK/NIDDK NIH HHS/ -- R01 DK60027-01/DK/NIDDK NIH HHS/ -- T32CA70083-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 15;298(5597):1395-401. Epub 2002 Oct 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section on Immunology and Immunogenetics, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12376594" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Autoantibodies/analysis/blood ; Autoantigens/biosynthesis/genetics ; Autoimmune Diseases/genetics/immunology/metabolism ; Autoimmunity ; Epithelial Cells/physiology ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Targeting ; Humans ; Lymphocytes/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Polyendocrinopathies, Autoimmune/genetics/immunology/metabolism ; Radiation Chimera ; Reverse Transcriptase Polymerase Chain Reaction ; *Self Tolerance ; Stromal Cells/immunology/metabolism ; T-Lymphocytes/*immunology ; Thymus Gland/cytology/*immunology/*metabolism ; Transcription Factors/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Diversity of endogenous epitopes bound to MHC class II molecules limited by invariant chain (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-03-04
    Description: The invariant chain (Ii) binds nascent major histocompatibility complex (MHC) class II molecules, blocking peptide binding until the complex dissociates in the endosomes. This may serve to differentiate the MHC class I and II antigen presentation pathways and enable class II molecules to efficiently bind peptides in the endosomes. This hypothesis was addressed by probing spleen cells from a combination of knock-out and transgenic mice with a large panel of T cell hybridomas. The Ii molecule blocked the presentation of a range of endogenously synthesized epitopes, but some epitopes actually required Ii. Thus, the influence of Ii on presentation does not follow simple rules. In addition, mice expressing Ii were not tolerant to epitopes unmasked in its absence, a finding with possible implications for autoimmunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bodmer, H -- Viville, S -- Benoist, C -- Mathis, D -- New York, N.Y. -- Science. 1994 Mar 4;263(5151):1284-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7510069" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigen-Presenting Cells/*immunology ; *Antigens, Differentiation, B-Lymphocyte ; Epitopes/*immunology ; Histocompatibility Antigens Class II/genetics/*immunology ; Hybridomas ; Mice ; Mice, Knockout ; Mice, Transgenic ; Molecular Sequence Data ; Myelin Basic Protein/immunology ; Recombinant Fusion Proteins/immunology ; T-Lymphocytes/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-03-21
    Description: Aire is an important regulator of immunological tolerance, operating in a minute subset of thymic stromal cells to induce transcripts encoding peptides that guide T cell selection. Expression of Aire during a perinatal age window is necessary and sufficient to prevent the multiorgan autoimmunity characteristic of Aire-deficient mice. We report that Aire promotes the perinatal generation of a distinct compartment of Foxp3(+)CD4(+) regulatory T (Treg) cells, which stably persists in adult mice. This population has a role in maintaining self-tolerance, a transcriptome and an activation profile distinguishable from those of Tregs produced in adults. Underlying the distinct Treg populations are age-dependent, Aire-independent differences in the processing and presentation of thymic stromal-cell peptides, resulting in different T cell receptor repertoires. Our findings expand the notion of a developmentally layered immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710357/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Siyoung -- Fujikado, Noriyuki -- Kolodin, Dmitriy -- Benoist, Christophe -- Mathis, Diane -- R01 DK060027/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2015 May 1;348(6234):589-94. doi: 10.1126/science.aaa7017. Epub 2015 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, South Korea. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA 02115, USA. cbdm@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25791085" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/analysis ; Autoimmunity ; Forkhead Transcription Factors/analysis ; Mice ; Mice, Knockout ; Receptors, Antigen, T-Cell/immunology ; Self Tolerance/*genetics ; T-Lymphocytes, Regulatory/*immunology ; Transcription Factors/genetics/*physiology ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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