The use of mouse models to better understand mechanisms of autoimmunity and tolerance.

Journal of Autoimmunity
Fumi MiyagawaStephen I Katz

Abstract

A major emphasis of our studies has been on developing a better understanding of how and why the skin serves as a target for immune reactions as well as how the skin evades becoming a target for destruction. For these studies we developed transgenic mice that express a membrane-tethered form of a model self antigen, chicken ovalbumin (mOVA), under the control of a keratin 14 (K14) promoter. K14-mOVA transgenic mice that express OVA mRNA and protein in the epithelia have been assessed for their immune responsiveness to OVA and are being used as targets for T cells obtained from OT-1 transgenic mice whose CD8+ T cells carry a Vα2/Vβ5-transgenic T cell receptor with specificity for the OVA(257-264)-peptides (OVAp) in association with class I MHC antigens. Some of the K14-mOVA transgenic mice develop a graft-versus-host-like disease (GvHD) when the OT-1 cells are injected while others appear to be tolerant to the OT-1 cells. We found that γc cytokines, especially IL-15, determine whether autoimmunity or tolerance ensues in K14-mOVA Tg mice. We also developed transgenic mice that express soluble OVA under the control of a K14 promoter (K14-sOVA) that die within 5-8 days after adoptive transfer of OT-1 cells and identified these mice...Continue Reading

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Citations

Jul 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Fumi MiyagawaStephen I Katz
Jan 15, 2013·Journal of Pharmaceutical Sciences·Nina BrendenAnn Lövgren
Aug 7, 2012·Journal of Autoimmunity·Christophe JaminJacques-Olivier Pers
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Jun 19, 2012·Journal of Autoimmunity·Zhigang TianCai Zhang
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