The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laufer, T. M.
Right arrow Articles by Glimcher, L. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laufer, T. M.
Right arrow Articles by Glimcher, L. H.
Right arrowPubmed/NCBI databases
Medline Plus Health Information
*Autoimmune Diseases
The Journal of Immunology, 1999, 162: 5078-5084.
Copyright © 1999 by The American Association of Immunologists

Self-Reactive T Cells Selected on Thymic Cortical Epithelium Are Polyclonal and Are Pathogenic In Vivo1

Terri M. Laufer2,*,{dagger}, Lian Fan3,* and Laurie H. Glimcher*,{dagger}

* Department of Immunology and Infectious Diseases, Harvard School of Public Health, and {dagger} Department of Medicine, Harvard Medical School, Boston, MA 02115

Positive selection of CD4+ T cells requires that the TCR of a developing thymocyte interact with self MHC class II molecules on thymic cortical epithelium. In contrast, clonal deletion is mediated by dendritic cells and medullary epithelium. We previously generated K14 mice expressing MHC class II only on thymic cortical epithelium. K14 CD4+ T cells were positively, but not negatively, selected and had significant in vitro autoreactivity. Here, we examine the function of these autoreactive CD4+ T cells in more detail. Analysis of a series of K14-derived T hybrids demonstrated that the autoreactive population of CD4+ T cells is phenotypically and functionally diverse. Purified K14 CD4+ T cells transferred into lethally irradiated wild-type B6 mice cause acute graft vs host disease with bone marrow failure. Further, these autoreactive CD4+ T cells cause hypergammaglobulinemia and the production of autoantibodies when transferred into unirradiated wild-type hosts. Thus, positive selection by normal thymic cortical epithelial cells, unopposed by negative selection, produces polyclonal CD4+ T cells that are pathologic.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
T. L. Stephen, A. Tikhonova, J. M. Riberdy, and T. M. Laufer
The Activation Threshold of CD4+ T Cells Is Defined by TCR/Peptide-MHC Class II Interactions in the Thymic Medulla
J. Immunol., November 1, 2009; 183(9): 5554 - 5562.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C. Ohnmacht, A. Pullner, S. B.S. King, I. Drexler, S. Meier, T. Brocker, and D. Voehringer
Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity
J. Exp. Med., March 16, 2009; 206(3): 549 - 559.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Ribot, G. Enault, S. Pilipenko, A. Huchenq, M. Calise, D. Hudrisier, P. Romagnoli, and J. P. M. van Meerwijk
Shaping of the Autoreactive Regulatory T Cell Repertoire by Thymic Cortical Positive Selection
J. Immunol., November 15, 2007; 179(10): 6741 - 6748.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Zhang, E. Hexner, D. Frank, and S. G. Emerson
CD4+ T Cells Generated De Novo from Donor Hemopoietic Stem Cells Mediate the Evolution from Acute to Chronic Graft-versus-Host Disease
J. Immunol., September 1, 2007; 179(5): 3305 - 3314.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y. Sakoda, D. Hashimoto, S. Asakura, K. Takeuchi, M. Harada, M. Tanimoto, and T. Teshima
Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease
Blood, February 15, 2007; 109(4): 1756 - 1764.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Bunin, F. W. Khwaja, and G. J. Kersh
Regulation of Bim by TCR Signals in CD4/CD8 Double-Positive Thymocytes
J. Immunol., August 1, 2005; 175(3): 1532 - 1539.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J.-F. Poulin, M. Sylvestre, P. Champagne, M.-L. Dion, N. Kettaf, A. Dumont, M. Lainesse, P. Fontaine, D.-C. Roy, C. Perreault, et al.
Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease
Blood, December 15, 2003; 102(13): 4600 - 4607.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Teshima, P. Reddy, C. Liu, D. Williams, K. R. Cooke, and J. L. M. Ferrara
Impaired thymic negative selection causes autoimmune graft-versus-host disease
Blood, July 15, 2003; 102(2): 429 - 435.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. Fan, B. W. Busser, T. Q. Lifsted, D. Lo, and T. M. Laufer
Antigen presentation by keratinocytes directs autoimmune skin disease
PNAS, March 18, 2003; 100(6): 3386 - 3391.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Xi and G. J. Kersh
Induction of the Early Growth Response Gene 1 Promoter by TCR Agonists and Partial Agonists: Ligand Potency Is Related to Sustained Phosphorylation of Extracellular Signal-Related Kinase Substrates
J. Immunol., January 1, 2003; 170(1): 315 - 324.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
O. Boyer, G. Marodon, J. L. Cohen, L. Lejeune, T. Irinopoulou, R. Liblau, P. Bruneval, and D. Klatzmann
Human CD4 Expression at the Late Single-Positive Stage of Thymic Development Supports T Cell Maturation and Peripheral Export in CD4-Deficient Mice
J. Immunol., October 15, 2002; 169(8): 4347 - 4353.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Romagnoli, D. Hudrisier, and J. P. M. van Meerwijk
Preferential Recognition of Self Antigens Despite Normal Thymic Deletion of CD4+CD25+ Regulatory T Cells
J. Immunol., February 15, 2002; 168(4): 1644 - 1648.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Y. Wu and I. Goldschneider
Tolerance to Cyclosporin A-Induced Autologous Graft-Versus-Host Disease Is Mediated by a CD4+CD25+ Subset of Recent Thymic Emigrants
J. Immunol., June 15, 2001; 166(12): 7158 - 7164.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Capone, P. Romagnoli, F. Beermann, H. R. MacDonald, and J. P. M. van Meerwijk
Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells
Blood, March 1, 2001; 97(5): 1336 - 1342.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Gaszewska-Mastalarz, P. Muranski, B. Chmielowski, P. Kraj, and L. Ignatowicz
Altered Selection of CD4+ T Cells by Class II MHC Bound with Dominant and Low Abundance Self-Peptides
J. Immunol., December 1, 2000; 165(11): 6099 - 6106.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Winer, L. Gunaratnam, I. Astsatourov, R. K. Cheung, V. Kubiak, W. Karges, D. Hammond-McKibben, R. Gaedigk, D. Graziano, M. Trucco, et al.
Peptide Dose, MHC Affinity, and Target Self-Antigen Expression Are Critical for Effective Immunotherapy of Nonobese Diabetic Mouse Prediabetes
J. Immunol., October 1, 2000; 165(7): 4086 - 4094.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
A. I. Caplan and J. E. Dennis
Genetically Linked Scientists: The One-Two Punch for Nfatp Knockout
J. Exp. Med., January 3, 2000; 191(1): 1 - 4.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1999 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1999 by The American Association of Immunologists, Inc. All rights reserved.