Transcription profiling of mouse MBP Ac 11-11 activated purified CD4+ T cells

Local catabolism of the amino acid tryptophan (Trp) by indoleamine-2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased upon stimulation of myelin-specific T cells with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory TH1 cytokines. N-(3,4,-dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating TH1-mediated autoimmune diseases, such as MS. 4Y vd 1-11 comparison files are available as supplementary files. Experiment Overall Design: Double stranded cDNA was generated from total RNA extracted from MBP Ac 11-11 activated purified CD4+ T cells. Biotinylated cRNA was manufactured by in vitro transcription and hybridized to the Affymetrix genechip murine Mu11k set according to the manufacturer's protocols. Results were calculated as the ratio of mean average differences for each gene in 4Y versus Ac1-11 stimulated samples.