W227 - Immune Profiling of γδ T Cells After Human Intestinal Transplantation Reveals Their Roles in Lymphohematopoietic Graft-vs-host Responses and Graft Rejection
Abstract Text: We performed phenotypic and clonal tracking of donor- and recipient-derived γδ T cells after human intestinal transplantation (ITx) in blood, intestinal graft and bone marrow (BM). We previously demonstrated that donor T cell macrochimerism (peak level ≥4% in blood) is associated with less rejection. Here we found that increased γδ blood chimerism was present in patients with higher levels of total T cell chimerism. Remarkably, donor γδ T cells were detected in recipient BM 105–357 days post-Tx. Single-cell profiling of BM-infiltrating donor γδ T cells from 3 pediatric donors revealed both Vδ1- and Vδ2-dominant clonotypes with cytotoxic effector phenotypes that might contribute to graft-vs-host responses. BM-infiltrating donor δ2+ T cells are dominated by sequences with zero N-additions that likely originate during fetal life and are shared across pediatric, but not adult, donors, suggesting an age-related distribution and migration pattern. In contrast to αβ T cells, the turnover dynamics of γδ T cells in the graft showed a stronger association with donor age than with the status of macrochimerism. Graft-repopulating recipient γδ T cells showed effector phenotypes early post-Tx and gradually developed into cytotoxic resident-memory T cells with “private” non-Vγ9δ2 clonotypes. In one patient, the top dominant Vδ2 sequence (mainly Vγ5δ2) in blood during quiescence was also the top dominant clone in later rejecting ileal graft samples, but with much lower frequencies in earlier quiescent grafts, indicating active crosstalk of γδ T cells between blood and intestinal grafts during rejection. γδ T cells may influence chimerism and rejection after ITx.
