Suppression of IGRP-specific CD8 T cells following induction of tolerance to a Hybrid Insulin Peptide CD4 neoepitope

Abstract An autoimmune-mediated death of insulin-producing beta cells, orchestrated by effector CD4 and CD8 T cells that recognize islet antigens, results in Type 1 Diabetes. A dominant autoantigen the NOD mouse model autoimmune diabetes is a neoepitope termed 2.5 Hybrid Insulin Peptide (2.5HIP). By delivering 2.5HIP as an antigen-specific immunotherapy on tolerogenic PLG-nanoparticles, grafts diabetic mice survived longer cytokine production autoreactive was suppressed, including well-studied IGRP tetramer+ (tet+) cells. Using both transplant recipients prediabetic treated with nanoparticles, we examined mechanisms peripheral tolerance induction to impact function Following 2.5HIP, there increase dysfunctional surface marker expression (PD1+ TIM3+) tet+ spleen mice. Along decrease function, observed fraction Treg Tr1 expressing IL10 islets, spleen, draining lymph nodes tolerized Concurrently, accumulated were less able traffic infiltrate islets. Of entered fewer cytolytic CX 3CR1 +effector The robust functional may provide potential mechanism for accumulation node explain their inefficient trafficking into, within, islets following induction. NIH - T32 5T32DK120520-03, R01 2R01DK081166-11) JDRF 2-SRA-2020-907-S-B