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Autoimmunity pp 285-294 | Cite as

Murine Models of Lupus Induced by Hypomethylated T Cells

  • Bruce Richardson
  • Donna Ray
  • Raymond Yung
Part of the Methods in Molecular Medicine™ book series (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.

Key Words

Animal models autoimmunity drug-induced lupus DNA methylation lupus 

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Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  • Bruce Richardson
    • 1
  • Donna Ray
    • 2
  • Raymond Yung
    • 1
  1. 1.Department of Internal MedicineUniversity of Michigan and the Ann Arbor Veteran’s Affairs HospitalAnn Arbor
  2. 2.Department of Internal MedicineUniversity of MichiganAnn Arbor

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