# T cell Heterogeneity and Fate Diversification in Autoimmune Type I Diabetes

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $51,036

## Abstract

Project Summary
Type I diabetes (T1D) is a T cell-mediated autoimmune disease which is dramatically increasing in incidence.
The pathogenesis of T1D is complex and incompletely understood, involving progressive destruction of
pancreatic insulin-producing b cells by CD8 T cells, which leads to insulin deficiency and loss of glucose
homeostasis. However, many aspects of the programming and regulation of self-reactive CD8 T cells mediating
autoimmunity remain enigmatic. Utilizing the clinically relevant non-obese diabetic (NOD) mouse model of T1D,
I investigated the activation and differentiation of b cell antigen-specific CD8 T cells throughout the course of
T1D. I found that antigen-specific CD8 T cells exhibited phenotypic heterogeneity in the pancreatic draining
lymph node (pLN) and in the pancreas. The specific hypothesis of this proposal is that the pancreatic
autoimmune CD8 T cell response in T1D is driven by heterogeneous populations arising in the pLN. In
this study, I will define the spatiotemporal factors that determine CD8 T cell population heterogeneity and identify
transcription factor networks that define distinct autoimmune T cell populations in the pLN and pancreas in T1D.
High-throughput RNA sequencing, in vivo gain and loss of function studies, and pharmacologic modulation
experiments will be performed to determine the phenotypic, functional, and molecular characteristics of antigen-
specific autoimmune CD8 T cells. Single-cell RNA sequencing will be employed to define population
heterogeneity. This proposal is tailored for a physician-scientist in training, as it investigates the molecular
mechanisms underlying a human disease and may identify promising molecular targets for the prevention or
treatment of T1D and other T cell-mediated autoimmune diseases.

## Key facts

- **NIH application ID:** 10227182
- **Project number:** 5F30DK122691-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Sofia Vaccarino Gearty
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-08-14 → 2023-08-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227182

## Citation

> US National Institutes of Health, RePORTER application 10227182, T cell Heterogeneity and Fate Diversification in Autoimmune Type I Diabetes (5F30DK122691-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10227182. Licensed CC0.

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