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Title: Murine models of lupus induced by hypomethylated T cells.

Authors: Richardson, Bruce; Ray, Donna; Yung, Raymond

Published In Methods Mol Med, (2004)

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 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.

PubMed ID: 15286391 Exiting the NIEHS site

MeSH Terms: Adoptive Transfer; Animals; Antibodies, Antinuclear/blood; Autoimmunity; Azacitidine/pharmacology; CD4-Positive T-Lymphocytes/drug effects; CD4-Positive T-Lymphocytes/immunology*; CD4-Positive T-Lymphocytes/metabolism*; Cell Line; DNA Methylation*; Disease Models, Animal; Female; Humans; Immunoglobulin G/blood; Immunoglobulin M/blood; Lupus Erythematosus, Systemic/etiology*; Lupus Erythematosus, Systemic/immunology; Lupus Erythematosus, Systemic/metabolism; Mice; Mice, Inbred AKR; Mice, Inbred DBA

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