METHOD OF INHIBITING THE PROLIFERATION OF T AND/OR B LYMPHOCYTES VIA DIMETHYLARGININE DERIVATIVES AND LYMPHOCYTES PROLIFERATION INHIBITOR

摘要

The present invention belongs to the technical field of immunotherapy. A method of using dimethylarginine derivatives to inhibit the proliferation of lymphocyte. ADMA, SDMA, and their derivative DMGV can inhibit T cells and/or B cells proliferation in vitro by inducing mitochondrial ROS. ADMA and SDMA can induce mitochondrial ROS generation by the action of alanine-glyoxylate aminotransferase 2 (AGXT2), which converts both ADMA and SDMA into dimethylguanidino valeric acid (DMGV) in the mitochondria. The dimethylarginine dimethylamino hydrolase (DDAH) inhibitor PD404182 also inhibits T cell proliferation by allowing more ADMA and SDMA to be converted to DMGV. As a clinical relevance, DMGV effectively treated arthritis in mice which was caused by activated T cells.