Deciphering the Contribution of γδ T Cells to Outcomes in Transplantation

Abstract

γδ T cells are a subpopulation of lymphocytes expressing heterodimeric T-cell receptors composed of γ and δ chains. They are morphologically and functionally heterogeneous, innate yet also adaptive in behavior, and exhibit diverse activities spanning immunosurveillance, immunomodulation, and direct cytotoxicity. The specific responses of γδ T cells to allografts are yet to be fully elucidated with evidence of both detrimental and tolerogenic roles in different settings. Here we present an overview of γδ T-cell literature, consider ways in which their functional heterogeneity contributes to the outcomes after transplantation, and reflect on methods to harness their beneficial properties.

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

“…Co-expression of CD45RO/RA in several clusters hints at local proliferative potential, and interactions with APC and Treg may be essential to control CD8+ T cells at the maternal-fetal interface. Furthermore, recently addressed contributions of TCRγδ T cells to transplantation outcomes and their role in HIV controllers (58,59) advocate for an unexplored functional role of TCRγδ T cell subsets in early and term pregnancy, which requires further exploration. B cell clusters expressing CD39, a marker involved in the activation of B cells to suppress T cells (60), might resemble regulatory B cells.…”

Donor γδT Cells Promote GVL Effect and Mitigate aGVHD in Allogeneic Hematopoietic Stem Cell Transplantation

“…aGVHD model: BALB/c recipient mice received lethal TBI (750cGy: 2 doses of 375cGy with 4 h interval) from a 137 Cs source. Three hours later, 1×10 7 BMCs plus 5×10 6 splenocytes from WT or TCR-d -/-C57BL/6 mice were intravenously injected into lethally irradiated BALB/c recipient. The survivals were observed, and the body weights and clinical scores were assessed every two or three days.…”

“…The purity of expanded gdT cells was more than 95%. 1×10 7 gdT/Vg1/Vg4 cells were adoptively transferred into the recipient mice on day 0 of allo-HSCT. The purified anti-mouse TCRgd antibody was purchased from BD Bioscience (San Diego, CA).…”

“…Donor αβT cells are thought to be the primary T cell subpopulation responsible for mediating GVHD and graft versus leukemia (GVL) responses during allo-HSCT ( 5 , 6 ). Nevertheless, a number of recent studies suggest that γδT cells might also play a critical role in mediating the outcomes of allo-HSCT ( 1 , 7 , 8 ).…”

Innate Immune Determinants of Graft-Versus-Host Disease and Bidirectional Immune Tolerance in Allogeneic Transplantation

“…Vδ2-T cells constitute the majority of circulating γδ-T cells [ 229 ]. Human γδ-T cells maintain a Vγ9 chain and mainly recognize phosphorylated non-peptide molecules that are metabolic intermediates of the isoprenoid biosynthesis pathway [ 229 , 230 ].…”