TLR agonists abrogate co-stimulation blockade-induced mixed chimerism and transplantation tolerance.
Biochemistry & Molecular Pharmacology
Department of Medicine, Division of Diabetes; Department of Pathology; Program in Molecular Medicine
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.
DOI of Published Version
Ann N Y Acad Sci. 2008 Dec;1150:149-51.
Annals of the New York Academy of Sciences
Miller DM, Thornley TB, Pearson T, Yamazaki M, Brehm MA, Rossini AA, Greiner DL. (2008). TLR agonists abrogate co-stimulation blockade-induced mixed chimerism and transplantation tolerance.. GSBS Student Publications. https://doi.org/10.1196/annals.1447.034. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1602