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sCD200 Present in Mice Receiving Cardiac and Skin Allografts Causes Immunosuppression In Vitro and Induces Tregs.
MedLine Citation:
PMID:  23380863     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: CD200 overexpression in transgenic mice increases skin, cardiac, and renal allograft survival. Elevated levels of soluble CD200 (sCD200) are found in the serum of cancer individuals. We investigated whether sCD200 levels increase in mice with prolonged graft survival.
METHODS: Control or CD200 BL/6 recipients of BALB/c cardiac or skin grafts received low-dose rapamycin (0.5 mg/kg) at 36-hr intervals, a dose shown previously not to augment the survival of control grafts or alter the host antigraft immunity or graft gene expression profiles. Separate groups received high-dose rapamycin (1.5 mg/kg). Serum was obtained at 8, 15, and 80 days after grafting and assayed for sCD200 (enzyme-linked immunosorbent assay), for the suppression of immunity in mixed leukocyte cultures (MLCs), for the induction of regulatory T cells able to suppress cytotoxic T lymphocyte induction in MLCs, and for the ability to transfer graft survival to naïve recipients.
RESULTS: Both CD200 and conventional mice with early enhanced graft survival had increased levels of sCD200 in serum, which induced Tr1 able to suppress MLCs. Suppression was abolished after passage of serum over a CD200 immunoadsorbent column. Dendritic cells maturing in the presence of sCD200 serum could induce populations of Foxp3 regulatory T cells able to suppress MLCs in vitro. In CD200 mice with long-term surviving cardiac (skin) allografts in the absence of continued transgene induction (>80 days [>35 days]), sCD200 levels returned to baseline, with no loss of grafts, but sera were unable to suppress MLCs in vitro. sCD200 serum adoptively transferred increased graft survival to naïve mice.
CONCLUSION: We conclude that monitoring sCD200 at early times after engraftment may predict allograft survival.
Authors:
Reginald Gorczynski; Zhiqi Chen; Ismat Khatri; Kai Yu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  95     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  442-7     Citation Subset:  IM    
Affiliation:
1 The Toronto Hospital, University Health Network, Toronto, Ontario, Canada. 2 Departments of Surgery and Immunology, University of Toronto, Toronto, Ontario, Canada. 3 Address correspondence to: Reginald Gorczynski, M.D., Ph.D., The Toronto Hospital, University Health Network, 2-805, MaRS Tower, 101 College Street, Toronto, Ontario, Canada M5G1L7.
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