# Inflammation-driven T Cell Responses and their Dichotomous Effect on Host Immunity

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $528,000

## Abstract

Project Summary
Memory CD8 T cells can be reactivated by a T cell receptor (TCR) signal, but also pro-inflammatory cytokines.
Reactivation in the absence of a TCR signal is referred to as bystander-activation and has been observed
across a wide range of different inflammatory processes, including infections, autoimmunity and cancer.
Bystander activated T cell exert effector function and secrete effector molecules such as granzyme B and
interferon gamma, which contribute to enhancing host immunity, but also exacerbate tissue damage and
prevent resolution of inflammation. The pro-inflammatory signals that elicit bystander activation have been
fairly well defined, but little is known regarding the regulatory signals that can inhibit or turn off effector function
by bystander activated memory CD8 T cells. In contrast, the mechanisms that negatively regulate effector
function of memory CD8 T cells that are reactivated in a TCR-dependent manner are well established. Our
preliminary data suggest that there are distinct regulatory mechanisms in place for memory CD8 T cells
reactivated by TCR- vs. cytokine-mediated signals. We specifically propose to study these mechanisms in the
context of tissue-based immune responses to determine how a perturbation of these regulatory systems
affects pathogen clearance, as well as tissue damage and re-establishing of tissue homeostasis. Ultimately,
our goal is to use the gained insights to develop strategies that will allow for therapeutic targeting of T cell-
mediated tissue damage.

## Key facts

- **NIH application ID:** 10894719
- **Project number:** 5R01AI123323-09
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Martin Prlic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $528,000
- **Award type:** 5
- **Project period:** 2016-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894719

## Citation

> US National Institutes of Health, RePORTER application 10894719, Inflammation-driven T Cell Responses and their Dichotomous Effect on Host Immunity (5R01AI123323-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10894719. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*