# Using donor dendritic cells to optimize GvHD and GvL in allogeneic stem cell transplantation

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $756,133

## Abstract

ABSTRACT: The overarching goal is to identify and enrich donor dendritic cell (DC) populations that reduce
graft-versus-host disease (GvHD) and improve survival after allogeneic bone marrow transplantation (allo-BMT).
Our proposal is grounded on published findings that the content of donor DC in the bone marrow graft and in the
blood of transplant recipients have significant impact on clinical outcomes, improving survival by decreasing
GvHD-mortality without increasing relapse. Preclinical data from murine BMT model systems also show that
donor plasmacytoid dendritic cells (pDC) from bone marrow but not G-CSF mobilized grafts improve survival by
decreasing the severity of GvHD. The ability of donor pDC to limit GvHD is dependent upon their expression of
chemokine receptors, cytokines, neuropeptides and catabolic enzymes, but it is not known whether the same
DC subset produces all these factors, or whether there are multiple sub-populations of DC, each with different
functions. Another key question is how homing of donor DC to lymphoid and GvHD-target organs regulates T
cell immunity including GvHD and graft-versus-leukemia (GvL). Answering these questions and identifying cost-
effective procedures for collecting grafts containing immune-regulatory DC will facilitate application of these
exciting observations to clinical practice. To progress towards our overall goal, we propose three specific aims:
Aim 1. To identify the phenotype and gene expression profile of the most potent immuno-regulatory
subset of donor DC present in bone marrow and other graft sources. Hypothesis: bone marrow contains
subsets of DC progenitors that secrete immune-regulatory interleukins and chemokines that limit GvHD by
facilitating the generation of donor-derived induced-Treg (iTreg).
Aim 2. To define the mechanism by which donor bone marrow DC progenitors limit GvHD without
affecting the GvL activity of donor T cells. Hypothesis: bone marrow contains a subset of DC progenitors
that limit GvHD by generating iT-reg from naïve donor T cells in GVHD target tissues while GvL is mediated
by donor T cells activated in secondary lymphoid organs.
Aim 3. To define a stem cell mobilization approach that yields an engrafting number of stem cells and
increased numbers of immuno-regulatory DC progenitors Hypothesis: treatment of donors with a short-
course of Flt3-L will increase the numbers of immune-regulatory donor DC and a single injection of plerixafor
will mobilize these DC and hematopoietic stem cells into the blood where they can be collected by apheresis.
Our work to define mechanisms by which DC regulate immunity in allo-BMT will inform broad fields of medicine.

## Key facts

- **NIH application ID:** 10052895
- **Project number:** 1R01AI145231-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Edmund K Waller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $756,133
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052895

## Citation

> US National Institutes of Health, RePORTER application 10052895, Using donor dendritic cells to optimize GvHD and GvL in allogeneic stem cell transplantation (1R01AI145231-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052895. Licensed CC0.

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