Alteration of γδ T cell subsets in non‐human primates transplanted with GGTA1 gene‐deficient porcine blood vessels

Abstract

AbstractBackgroundαGal‐deficient xenografts are protected from hyperacute rejection during xenotransplantation but are still rejected more rapidly than allografts. Despite studies showing the roles of non‐Gal antibodies and αβ T cells in xenograft rejection, the involvement of γδ T cells in xenograft rejection has been limitedly investigated.MethodsSix male cynomolgus monkeys were transplanted with porcine vessel xenografts from wild‐type (n = 3) or GGTA1 knockout (n = 3) pigs. We measured the proportions and T cell receptor (TCR) repertoires of blood γδ T cells before and after xenotransplant. Grafted porcine vessel‐infiltrating immune cells were visualized at the end of experiments.ResultsBlood γδ T cells expanded and infiltrated into the graft vessel adventitia following xenotransplantation of α‐Gal‐deficient pig blood vessels. Pre‐ and post‐transplant analysis of γδ TCR repertoire revealed a transition in δ chain usage post‐transplantation, with the expansion of several clonotypes of δ1, δ3, or δ7 chains. Furthermore, the distinctions between pre‐ and post‐transplant δ chain usages were more prominent than those observed for γ chain usages.Conclusionγδ TCR repertoire was significantly altered by xenotransplantation, suggesting the role of γδ T cells in sustained xenoreactive immune responses.