Tu181 - Donor γδ T Cells May Contribute to Lymphohematopoietic Graft-versus-host Responses After Human Intestinal Transplantation

Zhou Fang – Columbia University; Kevin Crosby – Columbia University; Katherine Long – Columbia University; Tyla Young – Columbia University; Zicheng Wang – Columbia University; Constanza Bay Muntnich – Columbia University; Alaka Gorur – Columbia University; Wenyu Jiao – Columbia University; Rebecca Jones – Columbia University; Qi Yan – Columbia University; Yufeng Shen – Columbia University; Prakash Satwani – Columbia University; Joshua Weiner – Columbia University; Mercedes Martinez – Columbia University; Tomoaki Kato – Columbia University; Jianing Fu – Columbia University

Abstract Text: Innate- and adaptive-like features of human γδ T cells are associated with Vγ9+δ2+ and non-Vγ9δ2 clonotypes, respectively. Despite their presence in the blood and many organs, the role of γδ T cells in transplantation is unclear. We performed phenotypic and clonal tracking of donor-derived γδ T cells after human intestinal transplantation (ITx) in blood, intestinal graft, and bone marrow (BM) by integrating flow cytometry and sequencing platforms. We previously demonstrated that patients with high levels of blood T cell chimerism had less rejection due to the migration of graft-derived graft-versus-host-reactive donor αβ T cells into the recipient blood and BM to mediate lymphohematopoietic graft-versus-host responses (LGVHR) which counteract the host-versus-graft response. Here we found that the level of blood γδ T cell chimerism correlated with total T cell chimerism. Donor γδ T cells were detected in recipient BM between post-operative day (POD)105–357. Single-cell RNA profiling of BM-infiltrating donor γδ T cells from 3 patients with pediatric donors revealed both Vδ1- and Vδ2-dominant clonotypes with cytotoxic effector phenotypes. In one patient, the top-dominant donor clone (Vγ8Vδ1) detected during peak blood T cell chimerism (POD8–20) was also predominant in recipient BM on POD126, with high cytotoxic (GZMB/PRF1/GNLY) but low proliferation (MKI67) and BM-homing (CXCR4) gene expression. BM-infiltrating donor δ2+ T cells were dominated by sequences with zero N-additions that likely originated during fetal life and were shared across pediatric, but not adult donors, suggesting an age-related distribution and migration pattern. γδ T cells may influence LGVHR and blood chimerism after ITx.