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. © 2012 Springer Science+Business Media New York.
CITATION STYLE
Richardson, B., Sawalha, A. H., Ray, D., & Yung, R. (2012). Murine models of lupus induced by hypomethylated T cells (DNA Hypomethylation and Lupus?). Methods in Molecular Biology, 900, 169–180. https://doi.org/10.1007/978-1-60761-720-4_8
Mendeley helps you to discover research relevant for your work.