TLR agonists abrogate co-stimulation blockade-induced mixed chimerism and transplantation tolerance.
Department of Medicine, Division of Diabetes; Department of Pathology; Program in Molecular Medicine
Medical Subject Headings
Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chimerism; Immunosuppressive Agents; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Knockout; Poly I-C; Receptor, Interferon alpha-beta; Skin Transplantation; Toll-Like Receptor 3; Toll-Like Receptor 4; Toll-Like Receptors; Transplantation Tolerance
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
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Citation: Ann N Y Acad Sci. 2008 Dec;1150:149-51.