# Immune profiling of γδ T cells after human intestinal transplantation

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $243,000

## Abstract

PROJECT SUMMARY
γδ T cells can recognize diverse antigens and exert disparate functions. The innate- and adaptive-like features
of human γδ T cells may be driven by differential γδ T cell receptor (TCR) repertoires, which can be shaped by
tissue compartmentalization, age and history of antigen exposure. Despite comprising a significant proportion
of resident T cells in many organs, including gut and liver, γδ T cells and their possible role in transplantation
outcomes are largely under‐researched. Our overarching goals are to elucidate the fundamental
mechanisms of how γδ T cells participate in allograft rejection and host defense after human intestinal
transplantation (ITx). We revealed that clinical outcomes after ITx are largely determined by the balance
between graft-versus-host (GvH) and host-versus-graft (HvG) alloreactivities, using an approach that identifies
alloreactive T cell clones following pre-Tx mixed lymphocyte reactions on the basis of TCRβ CDR3 high
throughput sequencing (TCRβ-seq). We showed that GvH-reactive αβ T cells, expanded from preexisting
donor resident memory T cells (TRM) after encountering rapidly-repopulating recipient antigen-presenting cells
in the graft mucosa, acquire effector T cell (Teff) functions and migrate into circulation and bone marrow (BM),
where they attenuate HvG responses, facilitate donor cell engraftment and control rejection. Using single cell
RNA-seq, we found that BM-infiltrating donor γδ T cells, dominated by “public” Vδ2 clonotypes, showed
cytotoxic Teff phenotypes similar to CD8 αβ T cells, suggesting their potential to also attenuate HvG reactions
and make space for donor hematopoietic stem and progenitor cell engraftment. We found that recipient γδ T
cells gradually populated the allograft, undergoing phenotypic changes from Teff to TRM, mainly with “private”
Vδ1 clonotypes. We hypothesize that γδ T cells not only participate in host defense against pathogens, but
also have the potential to modulate two-way alloresponses after human ITx. We now propose a study of
phenotypic and clonal tracking of human γδ T cells locally and systemically after ITx and further investigation of
their regulatory roles on alloreactivity and association with graft outcomes. We propose to pursue three
Specific Aims: To determine the chimerism, phenotype and clonotype of donor- (Aim 1) and recipient- (Aim 2)
derived γδ T cells in graft mucosa, circulation and BM by flow cytometry, mass cytometry and TCRγδ-seq. Bulk
TCRγδ-seq of pre-Tx unstimulated and ex vivo-stimulated γδ T cell repertoires and post-Tx γδ T cell
repertoires in the circulation, intestinal allograft and BM of ITx patients will be linked with single cell
transcriptional profiles of γδ T cell using the iRepertoire and 10x Genomics platforms (Aim 3). Our proposed
research will provide a deeper understanding of the mechanisms behind γδ T cell chimerism, maturation of
TRM features, and their modulatory roles on local and systemic alloresponses, facilit...

## Key facts

- **NIH application ID:** 10351494
- **Project number:** 1R21AI166069-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jianing Fu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $243,000
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10351494

## Citation

> US National Institutes of Health, RePORTER application 10351494, Immune profiling of γδ T cells after human intestinal transplantation (1R21AI166069-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10351494. Licensed CC0.

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