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Methods Mol Biol. 2012;900:169-80. doi: 10.1007/978-1-60761-720-4_8.

Murine models of lupus induced by hypomethylated T cells (DNA hypomethylation and lupus…).

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1
University of Michigan and the Ann Arbor Veteran's Affairs Hospital, Ann Arbor, MI, USA. brichard@umich.edu

Abstract

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 MHC-specific autoreactivity 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 pathologic significance of the autoreactivity induced by inhibiting T cell DNA methylation has been tested by treating murine T cells in vitro with drugs which 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 lupus-like disease. Further, transgenic mice with an inducible T cell DNA methylation defect also develop lupus-like autoimmunity. This chapter describes the protocols for inducing autoreactivity in murine T cells in vitro and for inducing autoimmunity in vivo using an adoptive transfer approach or transgenic animal models.

PMID:
22933069
DOI:
10.1007/978-1-60761-720-4_8
[Indexed for MEDLINE]
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