Establishment of an experimental model for MHC homo-to-hetero transplantation

Autor: Tomoki Murata, Hyuma Tsuji, Nanami Eguchi, Airi Sasaki, Ken-ichiro Seino, Ryo Otsuka, Haruka Wada, Tatsuo Kawai, Mizuho Itoh
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
Scientific Reports
ISSN: 2045-2322
Popis: Preventing rejection is a major challenge in transplantation medicine, even when using pluripotent stem cell-derived grafts. In iPS cell (iPSC)-based transplantation, to reduce the risk of rejection, it is thought to be optimal that preparing the cells from donors whose human leukocyte antigen-haplotype are homozygous. Generally, this approach is referred to as major histocompatibility complex (MHC) homo-to-hetero transplantation, which is MHC-matched but minor antigen-mismatched. To investigate the immune response in the MHC homo-to-hetero transplantation, we established a murine experimental system in which MHC-matched but minor antigen-mismatched tissue (skin) grafts were transplanted into MHC-heterozygous recipients. Unexpectedly, only minor antigen-mismatched grafts were rejected at the same time points as rejection of fully allogeneic grafts. A vigorous anti-donor type T cell response was detected in vitro and conventional immunosuppressants targeting T cell activation had limited effects on controlling rejection. However, anti-donor antibodies were not detected only in the minor antigen-mismatched transplantation. This murine transplantation model can be used to further analyze immunological subjects for MHC homo-to-hetero iPSC-based transplantation.
Databáze: OpenAIRE
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