Comparative analysis of the fate of donor dendritic cells and B cells and their influence on alloreactive T cell responses under tacrolimus immunosuppression |
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Authors: | Azhipa Olga Kimizuka Kei Nakao Atsunori Toyokawa Hideyoshi Okuda Toyokazu Neto Joao Seda Alber Sean M Kaizu Takashi Thomson Angus W Demetris Anthony J Murase Noriko |
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Institution: | Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA. |
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Abstract: | We have shown that tacrolimus (TAC)-induced liver allograft acceptance is associated with migration and persistence of donor B cells and dendritic cells (DC). To clarify whether these MHC class II+ leukocytes have favorable roles in inducing tolerance, we analyzed recipient T cell reactions after allogeneic B or DC infusion. LEW rat B cells localized exclusively in BN host B cell follicles without any direct contact with host T cells. While few donor DC migrated to T cell areas and marginal zones, they were captured by host APC, suggesting that allogeneic MHC class II+ cells may induce immune reactions via the indirect pathway. Although DC-infused non-immunosuppressed recipients showed enhanced ex vivo anti-donor responses, persistent in vitro donor-specific hyporeactivity was seen equally with donor DC or B cell infusion under TAC. The results indicate that donor MHC class II+ APC are capable of regulating recipient immune reactions under TAC. Possible involvement of the indirect pathway of allorecognition is discussed. |
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Keywords: | APC antigen-presenting cells BM bone marrow BN Brown Norway CMTMR 5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine CR chronic rejection DC dendritic cells FCS fetal calf serum LEW Lewis mAb monoclonal antibody PALS periarteriolar lymphoid sheath TAC tacrolimus Donor dendritic cells B cells Tacrolimus |
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