The murine mutation scurfy (sf) results in an antigen-dependent lymphoproliferative disease with altered T cell sensitivity - PubMed (original) (raw)
The murine mutation scurfy (sf) results in an antigen-dependent lymphoproliferative disease with altered T cell sensitivity
J L Zahorsky-Reeves et al. Eur J Immunol. 2001 Jan.
Free article
Abstract
The scurfy (sf) murine mutation results in a rapidly fatal lymphoproliferative disease, causing death by 26 days. Mature CD4+ T cells which tested hyperresponsive to T cell receptor (TCR) stimulation are involved. When sf was bred onto a transgenic line (DO11.10) in which 75 - 95 % of the T cells express TCR for ovalbumin (OVA) 323 - 339, sf / Y OVA mice had prolonged lifespans and less severe clinical symptoms compared to controls. However, sf / Y OVA mice eventually developed disease and died with manifestations similar to those of the original sf strain. The Rag1 knockout (KO) mouse, which cannot produce mature T (or B) cells without the addition of functional transgenes, was chosen for further breeding. The combination of Rag1 KO, the OVA transgene, and sf produced mice with 100 % of their mature DO11.10 alpha beta T cells reactive strictly to OVA peptide. None of these Rag1 - / - sf / Y OVA mice developed the scurfy disease. They retained central deletion capability in vivo, but demonstrated an altered in vitro response to OVA peptide. These results indicate that mice without TCR for endogenous antigens do not develop scurfy symptoms, and are consistent with the hypothesis that the sf mutation requires antigen stimulation to manifest disease, perhaps via altered TCR sensitivity.
Similar articles
- Cellular and molecular characterization of the scurfy mouse mutant.
Clark LB, Appleby MW, Brunkow ME, Wilkinson JE, Ziegler SF, Ramsdell F. Clark LB, et al. J Immunol. 1999 Mar 1;162(5):2546-54. J Immunol. 1999. PMID: 10072494 - CD4+CD8- T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse.
Blair PJ, Bultman SJ, Haas JC, Rouse BT, Wilkinson JE, Godfrey VL. Blair PJ, et al. J Immunol. 1994 Oct 15;153(8):3764-74. J Immunol. 1994. PMID: 7930593 - Transplantation of T cell-mediated, lymphoreticular disease from the scurfy (sf) mouse.
Godfrey VL, Rouse BT, Wilkinson JE. Godfrey VL, et al. Am J Pathol. 1994 Aug;145(2):281-6. Am J Pathol. 1994. PMID: 8053488 Free PMC article. - Expression and functional significance of CTLA-4, a negative regulator of T cell activation.
Kosmaczewska A, Ciszak L, Boćko D, Frydecka I. Kosmaczewska A, et al. Arch Immunol Ther Exp (Warsz). 2001;49(1):39-46. Arch Immunol Ther Exp (Warsz). 2001. PMID: 11266089 Review.
Cited by
- Emerging Functions of Regulatory T Cells in Tissue Homeostasis.
Sharma A, Rudra D. Sharma A, et al. Front Immunol. 2018 Apr 25;9:883. doi: 10.3389/fimmu.2018.00883. eCollection 2018. Front Immunol. 2018. PMID: 29887862 Free PMC article. Review. - The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System.
Luo A, Leach ST, Barres R, Hesson LB, Grimm MC, Simar D. Luo A, et al. Front Immunol. 2017 Apr 10;8:417. doi: 10.3389/fimmu.2017.00417. eCollection 2017. Front Immunol. 2017. PMID: 28443096 Free PMC article. Review. - IL-1R1 is expressed on both Helios(+) and Helios(-) FoxP3(+) CD4(+) T cells in the rheumatic joint.
Müller M, Herrath J, Malmström V. Müller M, et al. Clin Exp Immunol. 2015 Oct;182(1):90-100. doi: 10.1111/cei.12668. Epub 2015 Jul 30. Clin Exp Immunol. 2015. PMID: 26076982 Free PMC article. - The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4+Foxp3+ Regulatory T-Cells.
Ju ST, Sharma R, Gaskin F, Kung JT, Fu SM. Ju ST, et al. Biology (Basel). 2012 Apr 4;1(1):18-42. doi: 10.3390/biology1010018. Biology (Basel). 2012. PMID: 24832045 Free PMC article. - FOXP3 and scurfy: how it all began.
Ramsdell F, Ziegler SF. Ramsdell F, et al. Nat Rev Immunol. 2014 May;14(5):343-9. doi: 10.1038/nri3650. Epub 2014 Apr 11. Nat Rev Immunol. 2014. PMID: 24722479 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials