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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25833

Title: Rapamycin-induced Allograft Tolerance: Elucidating Mechanisms and Biomarker Discovery
Authors: Urbanellis, Peter
Advisor: Levy, Gary A.
Department: Immunology
Keywords: Transplantation
Tolerance
Regulatory T Cells
Rapamycin
Genomics
Biomarkers
Issue Date: 12-Jan-2011
Abstract: The long-term success of transplantation is limited by the need for immunosuppression; thus, tolerance induction is an important therapeutic goal. A 16-day treatment with rapamycin in mice led to indefinite graft survival of fully mismatched cardiac allografts, whereas untreated hearts were rejected after 8-10 days. Specific tolerance was confirmed through subsequent skin grafts and in vitro lymphocyte assays that showed recipient mice remained immunocompetent towards 3rd party antigens but were impaired in responding to donor antigens. Mechanisms that account for this tolerant state were then investigated. Splenic CD8+CD44+ memory T-cells were reduced in tolerant mice but had increased frequencies of the CD62LLO population. CD4+CD25+Foxp3+ regulatory T-cells were increased in tolerant mice. Through multiplex PCR, 4 regulatory T-cell related genes were found up-regulated and 2 proinflammatory genes were down-regulated in accepted hearts. This expression pattern may serve as a putative biomarker of tolerance in patients undergoing transplantation.
URI: http://hdl.handle.net/1807/25833
Appears in Collections:Master

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