Premium
TLR Agonists Abrogate Co‐stimulation Blockade‐Induced Mixed Chimerism and Transplantation Tolerance
Author(s) -
Miller David M.,
Thornley Thomas,
Pearson Todd,
Yamazaki Masahiro,
Brehm Michael A.,
Rossini Aldo A.,
Greiner Dale L.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1447.034
Subject(s) - blockade , transplantation , stimulation , pancreatic islets , immune tolerance , cd8 , immunology , islet , medicine , receptor , toll like receptor , pharmacology , immune system , innate immune system , diabetes mellitus , endocrinology
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.