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

Background: alpha Gal-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 alpha beta T cells in xenograft rejection, the involvement of gamma delta T cells in xenograft rejection has been limitedly investigated.Methods: Six 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 gamma delta T cells before and after xenotransplant. Grafted porcine vessel-infiltrating immune cells were visualized at the end of experiments.Results: Blood gamma delta T cells expanded and infiltrated into the graft vessel adventitia following xenotransplantation of alpha-Gal-deficient pig blood vessels. Pre- and post-transplant analysis of gamma delta TCR repertoire revealed a transition in delta chain usage post-transplantation, with the expansion of several clonotypes of delta 1, delta 3, or delta 7 chains. Furthermore, the distinctions between pre- and post-transplant delta chain usages were more prominent than those observed for gamma chain usages.Conclusion gamma: delta TCR repertoire was significantly altered by xenotransplantation, suggesting the role of gamma delta T cells in sustained xenoreactive immune responses.

Automated summary

The involvement of gamma delta T cells in xenograft rejection was investigated in a study on cynomolgus monkeys transplanted with vessel xenografts from pigs. The study found that the gamma: delta TCR repertoire was significantly altered post-xenotransplantation, suggesting the important role of gamma delta T cells in sustained xenoreactive immune responses.