|
|
Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2003-01-0266.
Submitted January 28, 2003
Accepted March 12, 2003
Impaired thymic negative selection causes autoimmune graft-versus-host disease
Takanori Teshima, Pavan Reddy, Chen Liu, Debra Williams, Kenneth R Cooke, and James L M Ferrara*
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA; Department of Pediatrics, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
Department of Internal Medicine II, Okayama University Graduate School of Medicine, Okayama, Japan
Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA
* Corresponding author; email: ferrara{at}umich.edu.
Animal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T cell repertoire. We investigated the requirements for the development of systemic autoimmune disease by using bone marrow chimeras that lacked expression of MHC class II on thymic antigen-presenting cells (APCs), leading to impaired negative selection. We found that impaired negative selection mediated by absence of MHC class II, but not MHC class I, permitted the development of systemic autoimmune disease that is indistinguishable from acute graft-versus-host disease (GVHD). Thymectomy prevented disease, confirming the causal association of the thymus with its development. Adoptive transfer of CD4+ T cells cause GVHD in secondary hosts only when they were irradiated, and co-transfer of peripheral CD4+ and CD8+ T cells from naive mice prevented the disease. These results demonstrate that impaired thymic negative selection can cause lethal autoimmune disease indistinguishable from acute GVHD in the context of a proinflammatory milieu when peripheral regulatory mechanisms are absent.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
E. Tivol, R. Komorowski, and W. R. Drobyski
Emergent autoimmunity in graft-versus-host disease
Blood,
June 15, 2005;
105(12):
4885 - 4891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Clave, V. Rocha, K. Talvensaari, M. Busson, C. Douay, M.-L. Appert, C. Rabian, M. Carmagnat, F. Garnier, A. Filion, et al.
Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation
Blood,
March 15, 2005;
105(6):
2608 - 2613.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Rodriguez-Galan, J. H. Bream, A. Farr, and H. A. Young
Synergistic Effect of IL-2, IL-12, and IL-18 on Thymocyte Apoptosis and Th1/Th2 Cytokine Expression
J. Immunol.,
March 1, 2005;
174(5):
2796 - 2804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. Clark, R. Gregg, K. Piper, D. Dunnion, L. Freeman, M. Griffiths, G. Begum, P. Mahendra, C. Craddock, P. Moss, et al.
Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells
Blood,
March 15, 2004;
103(6):
2410 - 2416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
