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Factors governing the activation of adoptively transferred donor T cells infused after allogeneic bone marrow transplantation in the mouse.

ABSTRACT: Murine models of bone marrow transplantation were used to study the mechanisms governing the activation of donor lymphocyte infusions (DLIs) manifesting as lymphohematopoietic graft-versus-host (LH-GVH) and graft-versus-leukemia (GVL) reactivities. We demonstrate here that established mixed chimerism influences the potency of DLI-mediated alloreactivity only in the MHC-mismatched but not MHC-matched setting. In the MHC-matched setting, high levels (>or= 40%) of residual host chimerism correlated negatively with DLI-mediated alloreactivity irrespective of the timing of their administration, the donor's previous sensitization to host antigens, or the level of residual host APCs. In vivo administration of Toll-like receptor (TLR) ligands was required to maximize DLI-mediated LH-GVH and GVL reactivities in chimeras with low levels (

SUBMITTER: Durakovic N

PROVIDER: S-EPMC1885486 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Factors governing the activation of adoptively transferred donor T cells infused after allogeneic bone marrow transplantation in the mouse.

Durakovic Nadira N Radojcic Vedran V Skarica Mario M Bezak Karl B KB Powell Jonathan D JD Fuchs Ephraim J EJ Luznik Leo L

Blood 20070116 10

Murine models of bone marrow transplantation were used to study the mechanisms governing the activation of donor lymphocyte infusions (DLIs) manifesting as lymphohematopoietic graft-versus-host (LH-GVH) and graft-versus-leukemia (GVL) reactivities. We demonstrate here that established mixed chimerism influences the potency of DLI-mediated alloreactivity only in the MHC-mismatched but not MHC-matched setting. In the MHC-matched setting, high levels (>or= 40%) of residual host chimerism correlated ...[more]

PMID: 17227829

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