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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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Chimerism / drug effects*
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Immunosuppressive Agents / pharmacology*
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / drug effects*
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Lymphocyte Activation / immunology
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Mice
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Mice, Knockout
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Poly I-C / pharmacology
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Receptor, Interferon alpha-beta / genetics
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Skin Transplantation / immunology
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Skin Transplantation / veterinary
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Toll-Like Receptor 3 / agonists
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Toll-Like Receptor 4 / agonists
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Toll-Like Receptors / agonists*
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Transplantation Tolerance / drug effects*
Substances
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Ifnar1 protein, mouse
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Immunosuppressive Agents
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Lipopolysaccharides
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TLR3 protein, mouse
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Tlr4 protein, mouse
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Toll-Like Receptors
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Receptor, Interferon alpha-beta
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Poly I-C