Novel strategy for induction of tolerance in mouse models of T1D

  • Cantero, Judith Agudo J.A. (PI)

Project Details

Description

Professional antigen presenting cells (APCs) are immune cells, whose role is to uptake proteins (antigen) and show them to the effector cells of the immune system, the T cells. When these antigens belong to viruses or bacteria, the APCs present these antigens to the T cells in parallel with danger signals so the T cells know they must kill anything that possess such antigens. Conversely, some type of these APCs have a different job: they uptake antigens from the normal cells of the body and they present them to the T cells in a way that teaches the T cells that those antigens are indeed self-antigens and they shouldn’t attack the cells displaying them. This process is called “immune tolerance”. However, for not totally understood reasons, sometimes the APCs present self-antigens in the wrong way to the T cells and those kill any cell with those antigens. This process is the basis of type 1 diabetes. The APCs present antigens from the beta-cells (the insulin producing cells) to the T cells along with activation (danger) signals and the T cells destroy the beta-cells in a similar way to how they would kill infected or cancer cells.In our project we aim to characterize this type of APCs that are capable of showing antigens in a “tolerogenic” way. We will transfer beta-cell antigens exclusively to those tolerogenic APCs so they can re-teach the T cells that those are self-antigens and stop the autoimmune attack. For this purpose, we will generate gene-based vectors that can allow the presence of the antigen in the right type of APCs while will prevent the expression of the antigen in any other type (mostly the one inducing the immune response). This specificity represents a key advance compared to traditional vaccines (with little specificity), which results in a much higher safety profile. This will be achieved by exploiting endogenous regulatory molecules that show different patterns in different subsets and activation states of APCs.

StatusFinished
Effective start/end date1/03/1329/02/16

Funding

  • Juvenile Diabetes Research Foundation United States of America: $161,769.00

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