Tu189 - Expansion of EBV Peptide-specific CD8 T Cells from Multiple Sclerosis Patients and Healthy Donors Reveals Dysregulation of Effector Responses That May Be Associated with Disease Pathogenesis

William Frazier, M.D. – Fellow, VID/NINDS/NIH; Lauren Suarez – NexImmune, Inc; Maria Monaco Kushner, Ph.D. – VID/NINDS/NIH; Ruipeng Wang, Ph.D. – NexImmune, Inc; Mathias Oelke, Ph.D. – NexImmune, Inc; Steven Jacobson, Ph.D. – VID/NINDS/NIH

Abstract Text: Although 90% of adults are infected with EBV, recent studies have rekindled a role for this ubiquitous agent in the pathogenesis of MS. To assess whether Multiple Sclerosis (MS) is associated with defective T cell control of EBV-infected B cells, we employed a nanoparticle (np) based Artificial Immune Modulation (AIM) platform consisting of a cocktail of six EBV peptides presented on np decorated with HLA-A2 and anti-CD28 molecules to enrich, expand, and characterize EBV specific CD8+ T cells from healthy and MS HLA-A*02:01 donors. After 14 days, expanded cells were assessed for specificity and functionality as measured by intracellular cytokine staining and killing of EBV peptide loaded target cells. The expanded CD8+ T cells showed significant antigen specificity as shown by intracellular cytokine release and/or cytotoxic activity, which is consistent with previously published data. Interestingly, compared to heathy donors, such cells from MS patients exhibited functional defects in their responses to select EBV peptides. These results, analyzing the functional responses of EBV specific CD8 + T cells expanded from healthy donors and patients with MS, represent our initial effort to interrogate the hypothesis that MS may be associated with defective T cell control of EBV infected cells, which is consistent with a number of reports suggesting that a dysregulation of EBV specific immune responses is associated with the pathogenesis of MS creating potential opportunities for new therapeutic approaches in MS.