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    Ann N Y Acad Sci. 2008 Dec;1150:149-51.

    TLR agonists abrogate co-stimulation blockade-induced mixed chimerism and transplantation tolerance.

    Miller DM, Thornley T, Pearson T, Yamazaki M, Brehm MA, Rossini AA, Greiner DL.

    Source

    Department of Medicine, Division of Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

    Abstract

    We investigated the mechanisms by which Toll-like receptor (TLR) agonists affect the induction of mixed chimerism and skin allograft survival in mice treated with co-stimulation blockade (CB). We report that TLR agonists prevent the generation of mixed chimerism by breaking tolerance in the alloreactive CD4(+) and CD8(+) T cell compartments, and that type I interferon (IFN) is important in this process. Understanding how environmental perturbations affect CB-induced transplantation tolerance may lead to more effective regimens that can be used as an approach for the treatment of type I diabetes, for which the transplantation of pancreatic islets is a promising therapy.

    PMID:
    19120285
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2626129
    Free PMC Article

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