# Regulation of T cell activation and exhaustion by Tim-3

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $73,932

## Abstract

Abstract
The transmembrane protein Tim-3 is expressed on a subset of activated T cells, and is
particularly enriched on so-called exhausted T cells, which are associated with chronic viral
infection and the tumor microenvironment. As such, Tim-3 is being actively explored as a
potential target for tumor immunotherapy. However, significant questions remain about how
Tim-3 expression is regulated during acute vs. chronic infection, and how signaling
pathways downstream of Tim-3 modulate T cell function. Using LCMV infection, we have
found that Tim-3 expression and signaling augment early T cell activation during both
primary and recall responses, but that Tim-3 is dispensable for the development of T cell
exhaustion. Furthermore, we have found that the transcription factor Blimp1 can control
Tim-3 expression under some, but not all, circumstances. Here we will further define the
effects of Tim-3 on sculpting the overall CD4+ and CD8+ T cell responses to specific viral
epitopes of LCMV. We will also define the specific requirements for Blimp1 and
downstream factors, including the E-box binding factor inhibitor Id3. Finally, we will
determine the role of signaling through the cytoplasmic tail of Tim-3 in regulating T cell
activation, memory and exhaustion.

## Key facts

- **NIH application ID:** 10455832
- **Project number:** 3R01AI138504-04S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Lawrence P. Kane
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $73,932
- **Award type:** 3
- **Project period:** 2018-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455832

## Citation

> US National Institutes of Health, RePORTER application 10455832, Regulation of T cell activation and exhaustion by Tim-3 (3R01AI138504-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455832. Licensed CC0.

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