Recruitment of semiallogeneic dendritic cells to the thymus during post-cyclosporine thymic regeneration.
Based on studies of the thymic microenvironment in the model of cyclosporine (CsA)-associated syngeneic graft-versus-host disease, we have hypothesized that immune tolerance develops after CsA is stopped, as the thymus regenerates and recruits new dendritic cells. CsA normally induces medullary involution with destruction of the medullary dendritic cells (DC) and epithelium. This principle could provide practical advantages for transplantation if it is used to recruit new DC into the thymic medulla. Here we administer LEW x BN F1 splenocytes to BN rats and treat them with a short course of CsA. After CsA is stopped, the F1 cells are rapidly recruited to the thymus, and by 10 days after CsA, they are localized at the corticomedullary junction, the natural location of thymic DC. In contrast, dexamethasone, which induces cortical involution, did not lead to thymic recruitment of F1 DC. Recruitment was better if the splenocytes were administered before CsA was stopped. Engraftment of the thymus was also achieved using bone marrow and temporary skin grafts as sources of DC. These observations provide the basis for a novel approach to inducing tolerance to alloantigens with minimal immune suppression and define the goals for further development.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012038:Regeneration; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology
D007166:Immunosuppressive Agents; D016572:Cyclosporine