Peptide immunotherapies in Type 1 diabetes: lessons from animal models.

Abstract:

:Insulin dependent diabetes mellitus (Type 1 diabetes, T1D) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells by proinflammatory autoreactive T cells. In the past, several therapeutic approaches have been exploited by immunologists aiming to regulate the autoimmune response; this can occur by deleting lymphocyte subsets and/or re-establishing immune tolerance via activation of regulatory T cells. The use of broad immunosuppressive drugs was the first approach to be explored. Subsequently, antibody-based immunotherapies failed to discriminate between autoreactive versus non-autoimmune effectors. Antigen-based immunotherapy is a third approach developed to manipulate beta cell autoimmunity. This approach allows the selective targeting of disease-relevant T cells, while leaving the remainder of the immune system intact. Animal models have been successfully employed to prevent or treat T1D by injection of either the self proteins or peptides derived from them. Peptide immunotherapies have been mainly experimented in the NOD mouse spontaneous model of disease. In this review we therefore report the main approaches that rely on the use of peptides obtained from relevant autoantigens such as glutamic acid decarboxylase, isoform 65 (GAD65), insulin, proinsulin and islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP). Protective peptides have proven to be effective in treating or delaying the diabetic process. We also highlight the main difficulties encountered in extrapolating data to guide clinical translational investigations in humans.

journal_name

Curr Med Chem

authors

Fierabracci A

doi

10.2174/092986711794480230

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

577-86

issue

4

eissn

0929-8673

issn

1875-533X

pii

BSP/CMC/E-Pub/2011/ 036

journal_volume

18

pub_type

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