대한신장학회

논문분류	춘계학술대회 초록집
제목	Suppressive Effects of Anti-Mouse and Human C4d Chimeric Antigen Receptor Regulatory T Cells on Antibody-Mediated Rejection
저자	Sun-Kyung Lee
출판정보	2025; 2025(1):
키워드	ABO-incompatible transplantation, Antibody-mediated rejection, C4d, Chimeric antigen receptor, Regulatory T cells
초록	Deposition of complement component 4d (C4d) is a typical marker of antibody-mediated rejection (ABMR) or observed in majority of ABO-incompatible (ABOi) allografts. We developed both mouse and human anti-C4d chimeric antigen receptor (CAR) regulatory T cells (Tregs) to suppress ABMR. The anti-mouse C4d (mC4d) CAR Tregs were generated by retrovirally transducing the CAR construct into sorted CD4+CD62L+Foxp3+ Tregs. For murine ABMR models, hearts from human blood group A-transgenic BALB/c mice were transplanted into sensitized B6 mice. CD45.1+ non-transduced Tregs, irrelevant (control) CAR Tregs, or anti-mC4d CAR Tregs were transferred into the recipients. We also generated the anti-human C4d (hC4d) CAR, which consisted of anti-C4d scFv and human CD28 and CD3ζ signaling domains. The human CD4+CD45RA+CD127lowCD25+ Tregs were transduced with a lentiviral anti-hC4d CAR vector. A human ABMR model in a humanized mice was established by transplanting human skin into NSG mice, followed by the transfer of human peripheral blood mononuclear cells and sensitized plasma. Anti-mC4d CAR Tregs suppressed in vitro T cell proliferation similarly to control Tregs and significantly prolonged ABOi heart allograft survival compared to PBS control, non-transduced Tregs, and control CAR Tregs (P < 0.01). These Tregs reduced ABMR-related tissue injury and cytokine expression (IFN-γ, IL-6, IL-17) in heart allografts, with increased CD45.1+ Treg infiltration around C4d+ endothelial cells. Anti-hC4d CAR Tregs demonstrated similar in vitro suppressive activity and effectively suppressed ABMR in skin allografts in humanized mice (P < 0.01). They showed greater infiltration into C4d-deposited areas and significantly altered cytokine expression, with reduced pro-inflammatory cytokines (IFN-γ, IL-1β, TNF-α, IL-6) and increased IL-10 and TGF-β in skin allografts. Anti-C4d CAR Tregs can effectively suppress alloimmune responses in both mouse and human ABMR, highlighting their potential as a promising therapy for treating or preventing ABMR in allografts.
원문(PDF)	PDF 원문보기

간행물 검색

대한신장학회 회원관리 규정