# Induction of tolerance to a Hybrid Insulin Peptide and the impact on autoreactive T cell fate and function in autoimmune diabetic islet transplant

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2024 · $39,897

## Abstract

Project Summary/Abstract
 Type 1 Diabetes (T1D) is an autoimmune disease thought to be mediated by autoreactive CD4 and CD8
T cell that orchestrate the death of insulin-producing beta cells within pancreatic islets. This proposal aims to
investigate how antigen-specific immunotherapy (ASI) with a CD4-specific neoepitope can selectively suppress
autoreactive T cells by tolerogenic delivery of antigens in the NOD mouse model of autoimmune diabetes.
Previously, our lab demonstrated that induction of tolerance to a dominant CD4 neoepitope, the 2.5 Hybrid Insulin
Peptide (2.5HIP), can prolong islet graft survival in diabetic NOD mice. In the outlined studies, we will investigate
the mechanistic impact of ASI on the differentiation and function of effector CD4 and CD8 T cells in islet grafts.
The role of IL-10-producing regulatory T cells, expanded by 2.5HIP tolerance induction, will also be examined.
We hypothesize that induction of tolerance to the 2.5HIP expands antigen-specific IL10-producing regulatory T
cells that, directly or indirectly, arrest the effector differentiation and function of autoreactive CD4 and CD8 T
cells within islet grafts. The specific aims of the study are to (1) determine the differentiation and functional states
of antigen-specific CD4 and CD8 T cells following induction of tolerance to the hybrid insulin peptide, and (2)
determine the contribution of IL10-producing regulatory T cells to prolonged graft survival and the suppression
of autoreactive T cells. The completion of the proposed studies is expected to generate high-impact information
on the mechanisms underlying autoreactive T cell suppression and differentiation following induction of antigen-
specific tolerance. Findings from this research will also critically inform antigen-specific therapeutic approaches
for human T1D and other autoimmune diseases.

## Key facts

- **NIH application ID:** 10995525
- **Project number:** 1F31AI181452-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** James E DiLisio
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $39,897
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995525

## Citation

> US National Institutes of Health, RePORTER application 10995525, Induction of tolerance to a Hybrid Insulin Peptide and the impact on autoreactive T cell fate and function in autoimmune diabetic islet transplant (1F31AI181452-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995525. Licensed CC0.

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