# Specificity, Phenotype and Function of Pancreatic CD8 T Cells in Human Type 1 Diabetes

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $450,000

## Abstract

PROJECT SUMMARY
Human type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing
pancreatic beta cells. CD8 T cells are the most common [immune] cell found in insulitic lesions and are the
principal T cell type implicated in beta cell destruction. Studies performed within this project have already
revealed significant [and novel] findings including: 1) the first identification of auto-reactive CD8 T cells in the
islets of patients with T1D using a specially [designed method of] tetramer staining and 2) [the first description
of high] numbers of CD8 T cells infiltrating the exocrine pancreas in T1D patients compared with non-diabetic
individuals. Based on these findings, we anticipate that only a proportion of the cells that infiltrate the pancreas
are indeed auto-reactive. Thus, the pool of `bystander' CD8 T cells that recognize other, for example viral,
antigens might significantly contribute to the inflammatory environment of the organ. At present, the overall
specificities and frequencies of CD8 T cells in the pancreas and the cause for their entry and activation are not
fully understood. Possible targets are known autoantigens derived from beta cells such as insulin, IGRP, IA-2
and GAD (see Table 2 for abbreviations) and cellular matrix proteins, which could become presented [and
modified] when beta cells are destroyed, but viral proteins, for example enteroviral determinants are also
possible candidates. The overall objective of this renewal application is therefore to compare the
specificity, phenotype and function of CD8 T lymphocytes from human islets with those found in
exocrine tissue, and to assess whether their presence correlates with islet-specific pathology (e.g.
viral infections and their detectable footprints). We will study patients with recent-onset and longstanding
T1D in order to build a road map of specificities and to further understand how the relationship between the
CD8 T cell infiltrate and the disease course might evolve [both quantitatively and qualitatively over time. A
unique strength is not only the access to very unique organ repositories but also the newly established
collaboration with Dr. Alessandro Sette and Dr. Bjoern Peters' laboratories, which maintain the Immune
Epitope Database (IEDB) at La Jolla institute and are part of an epitope discovery initiative led by Novo
Nordisk. Using the information contained in the IEDB and in vitro assays, neo-epitopes to modified
autoantigens and new viral CD8 T cell epitopes restricted to HLA-A2 will be mapped and the information
shared with our laboratory. Overall, our findings should give us a better understanding of how and why T1D
develops and thus help ultimately with the development of new therapeutic options.]
Our first goal is to systematically and quantitatively detect autoreactive CD8 T cells within human islets and
exocrine pancreas and to correlate the number and activation status of these cells with the local
histopathology...

## Key facts

- **NIH application ID:** 9828555
- **Project number:** 5R01AI092453-09
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Matthias G. Von Herrath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,000
- **Award type:** 5
- **Project period:** 2011-05-02 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828555

## Citation

> US National Institutes of Health, RePORTER application 9828555, Specificity, Phenotype and Function of Pancreatic CD8 T Cells in Human Type 1 Diabetes (5R01AI092453-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828555. Licensed CC0.

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