# UNIQUE ROLES OF ANTIGEN PRESENTING CELLS ON T CELL TOLERANCE AND AUTOIMMUNITY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $431,227

## Abstract

7. Project Summary/Abstract
The development of both tolerance and autoimmunity is dependent on the presentation of self-antigens in the
thymus and periphery. Thymic tolerance requires recognition of self-antigens leading to negative selection, i.e.
deletion of self-reactive T cell clones; or selection into Foxp3+ regulatory T (Treg) cells, important for
maintaining immune homeostasis in the periphery. In the periphery, presentation of self-antigens results in
maintenance and induction of regulatory T cells to promote tolerance, but can also facilitate autoimmunity via
induction of self-reactive effector cells. These processes are driven by antigen presenting cells (APCs), of
which there are several subsets. Previously, we showed that Batf3-dependent CD8α+ DCs play an important
role in thymic tolerance as the major recipient of antigen transfer from medullary thymic epithelial cells
(mTECs), which produce a variety of self-antigens via the effect of the transcription factor Aire. Here, we
propose to continue our studies on the role of CD8α+ DCs in tolerance and autoimmunity. We will continue our
ongoing studies of thymic CD8α+ DCs with the goal of understanding the mechanisms of antigen transfer (Aim
1). We will also ask whether CD8α+ DCs present a unique array of self-antigens in the periphery with the goal
of identifying the origin of some of these antigens (Aim 2). Finally, we will determine whether peripheral CD8α+
DCs are involved in effector vs regulatory T cell differentiation in response to self-antigens (Aim 3). If
successful, this grant will offer new insights regarding the role of CD8α+ DCs in providing antigen-specific and
T cell developmental niches in the thymus and periphery that may control the balance between tolerance and
autoimmunity.

## Key facts

- **NIH application ID:** 9989004
- **Project number:** 5R01AI079187-13
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** CHYI S HSIEH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $431,227
- **Award type:** 5
- **Project period:** 2008-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989004

## Citation

> US National Institutes of Health, RePORTER application 9989004, UNIQUE ROLES OF ANTIGEN PRESENTING CELLS ON T CELL TOLERANCE AND AUTOIMMUNITY (5R01AI079187-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989004. Licensed CC0.

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