Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (121)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Smith, K. M.
Right arrow Articles by Hanahan, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, K. M.
Right arrow Articles by Hanahan, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

International Immunology, Vol 9, 1355-1365, Copyright © 1997 by Oxford University Press

ARTICLES

Pancreatic gene expression in rare cells of thymic medulla: evidence for functional contribution to T cell tolerance

KM Smith, DC Olson, R Hirose and D Hanahan
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0534, USA.

We report the initial characterization of rare cells within the thymus that express 'peripheral' self-antigens and are capable of inducing partial tolerance to a model protein. Mice from two transgenic families that express SV40 T antigen (Tag) in pancreatic islet beta cells under control of a rat insulin promoter (RIP) develop T cell tolerance toward this neo-self antigen. These mice express low levels of Tag mRNA in the thymus. Transplantation of thymus from tolerant RIP-Tag mice into athymic hosts is sufficient to confer tolerance by CD4+ Th cells and elicits variable tolerance by CD8+ cytotoxic T cells. Thymic medulla is shown to contain rare cells that express the endogenous insulin and somatostatin genes, and in the transgenic animals, Tag. These cells are referred to as 'peripheral antigen-expressing' (PAE) cells. Thymic cell fractionation reveals the PAE cells expressing insulin and Tag to be present in a fraction enriched for non-lymphoid, MHC class II+ cells. Notably, absence of thymic expression of the RIP-Tag gene in another transgenic family correlates with failure to establish self-tolerance and susceptibility to autoimmunity. Thus, expression of tissue- restricted genes such as insulin in PAE cells of thymic medulla may serve to limit development of potentially autoimmune T cells.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
J. Dooley, M. Erickson, and A. G. Farr
Lessons from Thymic Epithelial Heterogeneity: FoxN1 and Tissue-Restricted Gene Expression by Extrathymic, Endodermally Derived Epithelium
J. Immunol., October 15, 2009; 183(8): 5042 - 5049.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
T. Guo and M. Hebrok
Stem Cells to Pancreatic {beta}-Cells: New Sources for Diabetes Cell Therapy
Endocr. Rev., May 1, 2009; 30(3): 214 - 227.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
J. M. Gardner, J. J. DeVoss, R. S. Friedman, D. J. Wong, Y. X. Tan, X. Zhou, K. P. Johannes, M. A. Su, H. Y. Chang, M. F. Krummel, et al.
Deletional Tolerance Mediated by Extrathymic Aire-Expressing Cells
Science, August 8, 2008; 321(5890): 843 - 847.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Derbinski, S. Pinto, S. Rosch, K. Hexel, and B. Kyewski
Promiscuous gene expression patterns in single medullary thymic epithelial cells argue for a stochastic mechanism
PNAS, January 15, 2008; 105(2): 657 - 662.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Zhu, R. K. Chin, A. V. Tumanov, X. Liu, and Y.-X. Fu
Lymphotoxin Receptor Is Required for the Migration and Selection of Autoreactive T Cells in Thymic Medulla
J. Immunol., December 15, 2007; 179(12): 8069 - 8075.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
D. Hanahan, E. F. Wagner, and R. D. Palmiter
The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer
Genes & Dev., September 15, 2007; 21(18): 2258 - 2270.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. W. Hay and K. Docherty
Comparative Analysis of Insulin Gene Promoters: Implications for Diabetes Research
Diabetes, December 1, 2006; 55(12): 3201 - 3213.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
G. O. Gillard and A. G. Farr
The thymus: a house dividing
Blood, December 1, 2006; 108(12): 3629 - 3630.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. Narendran, A. M. Neale, B. H. Lee, K. Ngui, R. J. Steptoe, G. Morahan, O. Madsen, J. A. Dromey, K. P. Jensen, and L. C. Harrison
Proinsulin is encoded by an RNA splice variant in human blood myeloid cells
PNAS, October 31, 2006; 103(44): 16430 - 16435.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. O. Palumbo, D. Levi, A. A. Chentoufi, and C. Polychronakos
Isolation and Characterization of Proinsulin-Producing Medullary Thymic Epithelial Cell Clones
Diabetes, September 1, 2006; 55(9): 2595 - 2601.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Faideau, C. Lotton, B. Lucas, I. Tardivel, J. F. Elliott, C. Boitard, and J.-C. Carel
Tolerance to Proinsulin-2 Is Due to Radioresistant Thymic Cells
J. Immunol., July 1, 2006; 177(1): 53 - 60.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Dooley, M. Erickson, G. O. Gillard, and A. G. Farr
Cervical Thymus in the Mouse.
J. Immunol., June 1, 2006; 176(11): 6484 - 6490.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. O. Gillard and A. G. Farr
Features of Medullary Thymic Epithelium Implicate Postnatal Development in Maintaining Epithelial Heterogeneity and Tissue-Restricted Antigen Expression
J. Immunol., May 15, 2006; 176(10): 5815 - 5824.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
I. Durinovic-Bello, E. Jelinek, M. Schlosser, T. Eiermann, B. O. Boehm, W. Karges, L. Marchand, and C. Polychronakos
Class III Alleles at the Insulin VNTR Polymorphism Are Associated With Regulatory T-Cell Responses to Proinsulin Epitopes in HLA-DR4, DQ8 Individuals
Diabetes, December 1, 2005; 54(suppl_2): S18 - S24.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Dooley, M. Erickson, and A. G. Farr
An Organized Medullary Epithelial Structure in the Normal Thymus Expresses Molecules of Respiratory Epithelium and Resembles the Epithelial Thymic Rudiment of Nude Mice
J. Immunol., October 1, 2005; 175(7): 4331 - 4337.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. A. Garcia, K. R. Prabakar, J. Diez, Z. A. Cao, G. Allende, M. Zeller, R. Dogra, A. Mendez, E. Rosenkranz, U. Dahl, et al.
Dendritic Cells in Human Thymus and Periphery Display a Proinsulin Epitope in a Transcription-Dependent, Capture-Independent Fashion
J. Immunol., August 15, 2005; 175(4): 2111 - 2122.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
G. O. Gillard and A. G. Farr
Contrasting models of promiscuous gene expression by thymic epithelium
J. Exp. Med., July 5, 2005; 202(1): 15 - 19.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Daniel, C. Chiu, E. Giraudo, M. Inoue, L. A. Mizzen, N. R. Chu, and D. Hanahan
CD4+ T Cell-Mediated Antigen-Specific Immunotherapy in a Mouse Model of Cervical Cancer
Cancer Res., March 1, 2005; 65(5): 2018 - 2025.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
A. M. Gallegos and M. J. Bevan
Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation
J. Exp. Med., October 18, 2004; 200(8): 1039 - 1049.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. H. Hager, J. G. Hodgson, J. Fridlyand, S. Hariono, J. W. Gray, and D. Hanahan
Oncogene Expression and Genetic Background Influence the Frequency of DNA Copy Number Abnormalities in Mouse Pancreatic Islet Cell Carcinomas
Cancer Res., April 1, 2004; 64(7): 2406 - 2410.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
F. F. Shih, L. Mandik-Nayak, B. T. Wipke, and P. M. Allen
Massive Thymic Deletion Results in Systemic Autoimmunity through Elimination of CD4+ CD25+ T Regulatory Cells
J. Exp. Med., February 2, 2004; 199(3): 323 - 335.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Yan, T. Devos, L. Yu, G. Xia, O. Rutgeerts, J. Goebels, C. Segers, Y. Lin, M. Vandeputte, and M. Waer
Pathogenesis of Autoimmunity After Xenogeneic Thymus Transplantation
J. Immunol., June 15, 2003; 170(12): 5936 - 5946.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Zhang, M. S. Vacchio, B. P. Vistica, S. Lesage, C. E. Egwuagu, C.-R. Yu, M. P. Gelderman, M. C. Kennedy, E. F. Wawrousek, and I. Gery
T Cell Tolerance to a Neo-Self Antigen Expressed by Thymic Epithelial Cells: The Soluble Form Is More Effective Than the Membrane-Bound Form
J. Immunol., April 15, 2003; 170(8): 3954 - 3962.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Haribhai, D. Engle, M. Meyer, D. Donermeyer, J. M. White, and C. B. Williams
A Threshold for Central T Cell Tolerance to an Inducible Serum Protein
J. Immunol., March 15, 2003; 170(6): 3007 - 3014.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. P. Friday, S. L. Pietropaolo, J. Profozich, M. Trucco, and M. Pietropaolo
Alternative Core Promoters Regulate Tissue-specific Transcription from the Autoimmune Diabetes-related ICA1 (ICA69) Gene Locus
J. Biol. Chem., January 3, 2003; 278(2): 853 - 863.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
M. S. Anderson, E. S. Venanzi, L. Klein, Z. Chen, S. P. Berzins, S. J. Turley, H. von Boehmer, R. Bronson, A. Dierich, C. Benoist, et al.
Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein
Science, November 15, 2002; 298(5597): 1395 - 1401.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
S. Lesage, S. B. Hartley, S. Akkaraju, J. Wilson, M. Townsend, and C. C. Goodnow
Failure to Censor Forbidden Clones of CD4 T Cells in Autoimmune Diabetes
J. Exp. Med., November 4, 2002; 196(9): 1175 - 1188.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
X. Zheng, J.-X. Gao, H. Zhang, T. L. Geiger, Y. Liu, and P. Zheng
Clonal Deletion of Simian Virus 40 Large T Antigen-Specific T Cells in the Transgenic Adenocarcinoma of Mouse Prostate Mice: An Important Role for Clonal Deletion in Shaping the Repertoire of T Cells Specific for Antigens Overexpressed in Solid Tumors
J. Immunol., November 1, 2002; 169(9): 4761 - 4769.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. A. Chentoufi and C. Polychronakos
Insulin Expression Levels in the Thymus Modulate Insulin-Specific Autoreactive T-Cell Tolerance: The Mechanism by Which the IDDM2 Locus May Predispose to Diabetes
Diabetes, May 1, 2002; 51(5): 1383 - 1390.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. S. Wong, A. K. Moustakas, L. Wen, G. K. Papadopoulos, and C. A. Janeway Jr.
Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kd that stimulates CD8 T cells in insulin-dependent diabetes mellitus
PNAS, April 16, 2002; 99(8): 5551 - 5556.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
L. T. Nguyen, A. R. Elford, K. Murakami, K. M. Garza, S. P. Schoenberger, B. Odermatt, D. E. Speiser, and P. S. Ohashi
Tumor Growth Enhances Cross-Presentation Leading to Limited T Cell Activation without Tolerance
J. Exp. Med., February 11, 2002; 195(4): 423 - 435.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. Vafiadis, H. Ounissi-Benkalha, M. Palumbo, R. Grabs, M. Rousseau, C. G. Goodyer, and C. Polychronakos
Class III Alleles of the Variable Number of Tandem Repeat Insulin Polymorphism Associated with Silencing of Thymic Insulin Predispose to Type 1 Diabetes
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3705 - 3710.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. Efrat, D. Serreze, A. Svetlanov, C. M. Post, E. A. Johnson, K. Herold, and M. Horwitz
Adenovirus Early Region 3 (E3) Immunomodulatory Genes Decrease the Incidence of Autoimmune Diabetes in NOD Mice
Diabetes, May 1, 2001; 50(5): 980 - 984.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
D. Voehringer, C. Blaser, A. B. Grawitz, F. V. Chisari, K. Buerki, and H. Pircher
Break of T Cell Ignorance to a Viral Antigen in the Liver Induces Hepatitis
J. Immunol., September 1, 2000; 165(5): 2415 - 2422.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
W. Savino and M. Dardenne
Neuroendocrine Control of Thymus Physiology
Endocr. Rev., August 1, 2000; 21(4): 412 - 443.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
F. Alderuccio, V. Cataldo, I. R. van Driel, P. A. Gleeson, and B. H. Toh
Tolerance and autoimmunity to a gastritogenic peptide in TCR transgenic mice
Int. Immunol., March 1, 2000; 12(3): 343 - 352.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Ma, Y. Ke, Q. Li, and J. A. Kapp
Bovine and Human Insulin Activate CD8+-Autoreactive CTL Expressing Both Type 1 and Type 2 Cytokines in C57BL/6 Mice
J. Immunol., January 1, 2000; 164(1): 86 - 92.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Sospedra, X. Ferrer-Francesch, O. Dominguez, M. Juan, M. Foz-Sala, and R. Pujol-Borrell
Transcription of a Broad Range of Self-Antigens in Human Thymus Suggests a Role for Central Mechanisms in Tolerance Toward Peripheral Antigens
J. Immunol., December 1, 1998; 161(11): 5918 - 5929.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
L. Klein, T. Klein, U. Ruther, and B. Kyewski
CD4 T Cell Tolerance to Human C-reactive Protein, an Inducible Serum Protein, Is Mediated by Medullary Thymic Epithelium
J. Exp. Med., July 1, 1998; 188(1): 5 - 16.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. B. Smith, H. Watada, D. W. Scheel, C. Mrejen, and M. S. German
Autoregulation and Maturity Onset Diabetes of the Young Transcription Factors Control the Human PAX4 Promoter
J. Biol. Chem., November 17, 2000; 275(47): 36910 - 36919.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. S. Wong, A. K. Moustakas, L. Wen, G. K. Papadopoulos, and C. A. Janeway Jr.
Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2Kd that stimulates CD8 T cells in insulin-dependent diabetes mellitus
PNAS, April 16, 2002; 99(8): 5551 - 5556.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
J.-X. Gao, H. Zhang, X.-F. Bai, J. Wen, X. Zheng, J. Liu, P. Zheng, and Y. Liu
Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
J. Exp. Med., April 15, 2002; 195(8): 959 - 971.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.