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Murine Models of Lupus Induced by Hypomethylated T Cells

  • Protocol
Autoimmunity

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 102))

Summary

CD4+ T-cell DNA hypomethylation may contribute to the development of drug-induced and idiopathic human lupus. Inhibiting DNA methylation in mature CD4+ T cells causes autoreactivity specific to the major histocompatibility complex in vitro. The lupus-inducing drugs hydralazine and procainamide also inhibit T-cell DNA methylation and induce autoreactivity, and T cells from patients with active lupus have hypomethylated DNA and a similarly autoreactive T-cell subset. Further, T cells treated with DNA methylation inhibitors demethylate the same sequences that demethylate in T cells from patients with active lupus. The pathological significance of the autoreactivity induced by inhibiting T-cell DNA methylation has been tested by treating murine T cells in vitro with drugs that modify DNA methylation, then injecting the cells into syngeneic female mice. Mice receiving CD4+ T cells demethylated by a variety of agents, including procainamide and hydralazine, develop a lupuslike disease. This chapter describes the protocols for inducing autoreactivity in murine T cells in vitro and using the cells to induce autoimmunity in vivo.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan and the Ann Arbor Veteran’s Affairs Hospital, Ann Arbor, MI

    Bruce Richardson & Raymond Yung

  2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI

    Donna Ray

Authors
  1. Bruce Richardson
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  2. Donna Ray
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  3. Raymond Yung
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Editor information

Editors and Affiliations

  1. Departments of Medicine, Microbiology, and Immunology, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY

    Andras Perl MD, PhD

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© 2004 Humana Press Inc., Totowa, NJ

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Richardson, B., Ray, D., Yung, R. (2004). Murine Models of Lupus Induced by Hypomethylated T Cells. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Medicine™, vol 102. Humana Press. https://doi.org/10.1385/1-59259-805-6:285

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  • DOI: https://doi.org/10.1385/1-59259-805-6:285

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-231-5

  • Online ISBN: 978-1-59259-805-2

  • eBook Packages: Springer Protocols

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