A previously unknown T cell receptor (TCR) activation pathway dependent on the aryl hydrocarbon receptor conferring resistance to calcineurin inhibitors and mTOR inhibitors is disclosed, including application of this pathway to the diagnosis and treatment of certain disease states refractory to treatment with calcineurin inhibitors. This alternative TCR activation pathway uniquely exists in a subset of CD8 T cells expanded in the setting of chronic rejection or rheumatoid arthritis. Expansion of this newly discovered calcineurin and mTOR inhibitor resistant CD8 T cell subset in humans can be quantified by measuring levels of certain biomarkers in the circulating CD8 T cell pool, such as Pla2g4a, to diagnose disease states mediated thereby. Additionally, methods for diagnosing ongoing active inflammation mediated by this resistant CD8 T cell subset in either chronic rejection or rheumatoid arthritis are provided, which comprise measuring levels of the biomarker Scin in the circulating CD8 T cell pool.
