Alteration of γδ T cell subsets in non-human primates transplanted with GGTA1 gene-deficient porcine blood vessels
Sujin Lee#, Yun Shin Chung#, Kyo Won Lee, Miran Choi, Chung Hee Sonn, Won Jun Oh, Hun Gi Hong, Joohyun Shim, Kimyung Choi, Sung Joo Kim, Jae Berm Park, Tae Jin Kim*
Xenotransplantation
- Cynomolgus monkeys were transplanted with wild type (n = 3) and α-Gal-deficient (n = 3) porcine blood vessels. Blood samples were obtained before and after the xenotransplantation. Pathologic and immunofluorescence were performed with blood vessels.
- Whereas wild type blood vessels were rapidly rejected, α-Gal-deficient blood vessels persisted for a few months.
- However, blood γδ T cells chronically expanded and infiltrated into the graft vessel adventitia following xenotransplantation of α-Gal-deficient pig blood vessels.
- Blood γδ T cell receptor (TCR) repertoires were compared before and after the 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.
- The distinctions between pre- and post-transplant δ chain usages were more prominent than those observed for γ chain usages.
- We could observe multiple γδ TCR clones shared with human.
- This study was published in Xenotransplantation in December 2023.
▷ Figure
H&E staining showing acute rejection with wild type blood vessel transplantation (W3) and heavy lymphocytic infiltration in adventitia of αGal knockout vessels(G1-G3). PreTx = before transplantation, POD = post-operative days
Repertoire comparison showing relative frequencies with combinations of V and J segments from TRG and TRD chains. We also obtained complete TCR sequences.