Murine Models of Lupus Induced by Hypomethylated T Cells (DNA Hypomethylation and Lupus)
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.
- 免疫球蛋白 D(immunoglobulin D, IgD)
- 立克次体、衣原体、支原体、螺旋体感染标本的采集与送检
- 类毒素(toxoid)
- 以蛋白分子为靶目标的噬菌体肽库筛选的常规实验方法
- 治疗基因
- The Activity of rRNA Resistance Methyltransferases Assessed by MALDI Mass Spectrometry
- Overview of Confocal Microscopy
- Multiplex PCR for the Rapid Simultaneous Speciation and Detection of Methicillin-Resistance and Genes Encoding Toxin Production
- Mammalian Cell Surface Display of Full Length IgG
- CD45/CD45RA/CD45RB/CD45RC/CD45RO