# CD27/CD70 mediated negative regulation of inflammatory T cell responses

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $586,090

## Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for a variety of
hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) remains the major
complication that causes significant morbidity and mortality despite the currently practiced immunosuppressive
therapies. GVHD is known to be caused by donor-derived T cells that recognize allogeneic antigens expressed
on host cells and subsequently damage host normal tissues. In addition to TCR signaling stimulated by MHC-
antigen complex, co-stimulatory pathways are involved in T cell activation and function. The co-stimulatory
molecule CD27 is a TNF receptor family member expressed on T cells and its ligand, CD70, is known to be
expressed on activated antigen-presenting cells (APC) as well as T cells. Previous studies using mainly viral
infection models have largely described this pathway as “stimulatory” and required for optimal T cell
responses, while its role in allo-HCT is previously unknown. In this project, we have used established murine
models to study the roles of CD27/CD70 in GVHD. Our results reveal a novel inhibitory role played by this
pathway as specified in 2 aspects: 1) allo-HCT shows that both CD27-/- and CD70-/- donor T cells caused more
severe GVHD than WT donor T cells, suggesting that CD27/CD70 signaling in donor T cells inhibits allogeneic
T cell response; 2) when used as hosts for allo-HCT, both CD27-/- and CD70-/- mice exhibited more severe
GVHD compared to WT hosts, suggesting that CD27/CD70 signaling in the host inhibits allogeneic T cell
response. Initial mechanistic analyses suggest that this pathway inhibits GVHD by limiting donor T cell
expansion and reducing pro-inflammatory cytokines in a donor regulatory T cell-independent fashion. Based on
these results, our central hypothesis is that CD27/CD70 signaling plays a novel role suppressing GVHD by
inhibiting allogeneic inflammatory T cell response. We propose three aims to systematically pursue donor T
cell-derived mechanisms, host-derived mechanisms and clinical relevance of this pathway in the context of
GVHD. Understanding such mechanisms will be critical for developing innovative strategies that can control
GVHD and improve quality of life for allo-HCT patients.

## Key facts

- **NIH application ID:** 9939675
- **Project number:** 5R01HL135325-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Xuefang Cao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $586,090
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939675

## Citation

> US National Institutes of Health, RePORTER application 9939675, CD27/CD70 mediated negative regulation of inflammatory T cell responses (5R01HL135325-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939675. Licensed CC0.

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