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Delayed Rejection of Xenograft (DRX)

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Glycoimmunology in Xenotransplantation
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Delayed rejection in organ transplantation is observed in a delayed type of immune rejection within a few hours to days after transplantation [1]. The delayed rejection is similar to the HR in its course and process. Human NK cells and CTLs are the major actors of delayed xenograft rejection (DRX) by cell mediation, but the DRX event is still in question [2]. DC is a regulator in anti-pig T-cell responses of human [2, 3]. The plasticity of DCs produces regulatory DCs, termed tolerant DCs, from undifferentiated progenitor cells such as CD14+ monocytes through differentiation induction by cytokines of IL-4 and GM-CSF. Regulatory DCs weakly express costimulatory proteins with the high ratio of the secreted IL-10/IL-12. They induce the CD4+ T-cell anergy state and the CD4-T regulatory cells (Tregs) expansion state that is antigen-specific [4, 5]. Human regulatory DCs can promote donor-specific tolerance in transplantation without any effect on the entire immune system [6]. Regulatory DC-based immune-regulatory therapies are recommended as adjunct immunosuppressive therapy treatments in transplant recipients. DCs mediate interaction between cells and release of cytokines as well as IFN-γ-acted CTL and NK cell activation and cytotoxicity. DCs’ interplay between innate and acquired immune responses initiates or modulates the immune responses. In xenoantigenic rejection, DCs activate NK cell and CTL to cell-mediated inflammatory and xenoreactive responses. Thus, differentiated regulatory DCs can be utilized to protect pig EC from human cell-mediated immune reaction. Regulatory DCs of human can decrease xenoantigenic responses of NK cells and CTLs to ECs of pig [7].

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Kim, CH. (2024). Delayed Rejection of Xenograft (DRX). In: Glycoimmunology in Xenotransplantation. Springer, Singapore.

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