Journal article

Perinatal tolerance to proinsulin is sufficient to prevent autoimmune diabetes

Gaurang Jhala, Jonathan Chee, Prerak M Trivedi, Claudia Selck, Esteban N Gurzov, Kate L Graham, Helen E Thomas, Thomas WH Kay, Balasubramanian Krishnamurthy

JCI INSIGHT | AMER SOC CLINICAL INVESTIGATION INC | Published : 2016

Abstract

High-affinity self-reactive thymocytes are purged in the thymus, and residual self-reactive T cells, which are detectable in healthy subjects, are controlled by peripheral tolerance mechanisms. Breakdown in these mechanisms results in autoimmune disease, but antigen-specific therapy to augment natural mechanisms can prevent this. We aimed to determine when antigen-specific therapy is most effective. Islet autoantigens, proinsulin (PI), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) were expressed in the antigen-presenting cells (APCs) of autoimmune diabetes-prone nonobese diabetic (NOD) mice in a temporally controlled manner. PI expression from gestation un..

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