# Mechanisms and consequences of T cell inflammasome activation in Graft-Versus Host Disease

> **NIH NIH R21** · LOYOLA UNIVERSITY CHICAGO · 2022 · $192,500

## Abstract

Graft Versus Host Disease (GVHD) remains a significant issue in people receiving hematopoietic
cell transplants to treat various cancers, genetic immunodeficiencies and other diseases. In
GVHD, alloreactive T cells mediate this pathology, as T cell depleted hematopoietic transplants
to not induce GVHD. We have observed that following transplantation, donor CD8 T cells
undergo inflammasome activation, as measured by the activation of caspase‐1. However, these
cells do not die via pyroptosis, which may alleviate their cytotoxic consequences in the host. We
also observe that these cells in which the inflammasome is activated hyperexpress a protein,
Ifi202, which is known to attenuate inflammasome activation, and human T cells similarly
express IFI16, which functions similarly in human cells. We hypothesize that Ifi202 limits the
degree of caspase‐1 activation in these cells, and thus prevents these cells from undergoing
pyroptosis. The goal of this project is to determine the mechanism of inflammasome activation
in these T cells, and to determine the role of Ifi202 in preventing pyroptosis in CD8 T cells
during GVHD. We hypothesize that reduced Ifi202 expression in these cells will attenuate GVHD
pathology by increasing pyroptosis in alloreactive CD8 T cells.

## Key facts

- **NIH application ID:** 10511777
- **Project number:** 1R21AI171879-01
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Edward M. Campbell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,500
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511777

## Citation

> US National Institutes of Health, RePORTER application 10511777, Mechanisms and consequences of T cell inflammasome activation in Graft-Versus Host Disease (1R21AI171879-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10511777. Licensed CC0.

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