# Local regulation and deletion of T cells to induce tolerance and establish long-term survival of high-risk corneal transplants

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $44,785

## Abstract

This application requests the NEI diversity research supplement funding to an active NEI grant (NEI:
#EY030283) in response to PA-21-071, to support the research training and career development of a graduate
student from an underprivileged racial/ethnic and economic background. In the proposed diversity supplement,
a predoctoral graduate student will lead a specific project that is directly relevant and complementary to - yet
clearly distinct from - the parent NEI award. The diversity supplement proposal is tailored for the graduate
student’s interest to understand how FoxP3+ T regulatory cells (Tregs) cells interact with the process of
conventional T cell exhaustion. Tregs are a non-redundant CD4 T cell population required for the maintenance
of self-tolerance. Additionally, the lack of functional Tregs has been demonstrated to result in
lymphoproliferation and pathology. Our group has discovered a novel strategy to manipulate Treg cells in vivo.
Tregs constitutively express the TNFRSF25 receptor, and we have learned that using agonists which target
and signal this receptor in combination with low doses of IL-2 administered in vivo, induce a rapid and marked
increase in the peripheral Treg compartment. Hence, this approach provides a unique tool to directly address a
key unanswered question in the transplant field central to the process of tolerance and rejection: do Tregs
impact the process of T cell exhaustion. This question is critical to develop a novel strategy to prevent
allografted tissue rejection, that is driving transplant antigen specific T cells to exhaustion. Specifically, while
undergoing research training and career development mentoring, the graduate student will learn to employ
rigorous scientific reasoning and multiple technologies to address the follow two questions: 1) Do activated
Treg cells prior/during induction of antigen specific CD8 T cells alter the exhaustion process? and 2) Can Treg
cells prolong rejection while CD8 exhaustion is driven by antigen? The student will take a well-crafted
curriculum designed for PhD training as well as participate in well-orchestrated career skill activities. The
student will work with a mentoring team to develop an individual career development plan (IDP) and
individualized mentoring plan (IMP) to guide him through the training process towards becoming independent
and a creative scholar conducting interdisciplinary research in immunology and transplantation. Through the
research and career training, the student is expected to be not only endowed to advance their own scientific
career, but also well-prepared to face emerging challenges with creative solutions and scientific
professionalism to advance society.

## Key facts

- **NIH application ID:** 10655894
- **Project number:** 3R01EY030283-03S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Robert Benjamin Levy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $44,785
- **Award type:** 3
- **Project period:** 2020-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10655894

## Citation

> US National Institutes of Health, RePORTER application 10655894, Local regulation and deletion of T cells to induce tolerance and establish long-term survival of high-risk corneal transplants (3R01EY030283-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10655894. Licensed CC0.

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