Latent EBV enhances the efficacy of teplizumab in Type 1 diabetes 3614

Abstract Description Teplizumab is approved for delay of diagnosis of type 1 diabetes and modulates new onset disease. Compared to EBV seronegative patients, those who were EBV seropositive prior to treatment had a more robust response to drug in two clinical trials. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and “partially exhausted” CD8+ T cells were found in EBV seropositive individuals at the baseline in the TN10 and AbATE trials. Single cell transcriptomics and functional assays identified downregulation of NFkB and other pathways after treatment in treated EBV seropositive patients. Among diabetes antigen specific CD8+ T cells, T cell receptor and mTOR signaling were also reduced. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways in immune cells, that broadly redirect cell differentiation Funding Sources Supported by grants DK057846 and AI66387 to KH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI109565. Topic Categories Translational and Interventional Immunology (TI)