Eur J Immunol 2005,
PMID: 15864782
Klingenberg, Roland; Autschbach, Frank; Gleissner, Christian; Giese, Thomas; Wambsganss, Nadine; Sommer, Natascha; Richter, Guenther; Katus, Hugo A; Dengler, Thomas J
The role of costimulatory molecules other than CD80/CD86 in endothelial cell (EC)-dependent CD8(+) T cell activation including the generation of a distinct subset of endothelium-specific CTL (EC-CTL) remains unclear. Inducible costimulator (ICOS) and its ligand (ICOSL) are new members of the CD28 family mediating effector T cell differentiation and graft rejection in animal models. In this study endothelial ICOSL expression/regulation and effects on CD8(+) T cell allo-activation were analyzed. Constitutive expression of ICOSL was found on human EC. IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB-dependent manner on human umbilical vein endothelial cells (HUVEC). ICOS receptor was not detected on resting CD8(+) T cells but was induced in co-cultures with HUVEC. ICOSL blockade reduced CD8(+) T cell proliferation by 70% along with a marked decrease of IL-2 and IFN-gamma production in co-cultures with HUVEC. IL-2 supplementation of co-cultures could overcome the effect of ICOSL blockade; similarly the generation of EC-CTL was not impaired by ICOSL blockade in an IL-2-containing system. In vivo, weak constitutive ICOSL expression was found on coronary microvessels, which was significantly up-regulated during acute cardiac allograft rejection (p=0.04). Our data indicate a distinct role for ICOSL in EC-mediated CD8(+) T cell costimulation with implications for human cardiac allograft rejection.
Diseases/Pathways annotated by Medline MESH: Acute Disease
Document information provided by NCBI PubMed
Text Mining Data
TNF-alpha → ICOSL: "
IL-1alpha and
TNF-alpha induced
ICOSL in an NF-kappaB dependent manner on human umbilical vein endothelial cells ( HUVEC )
"
ICOSL → IL-1alpha: "
IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB dependent manner on human umbilical vein endothelial cells ( HUVEC )
"
TNF-alpha — NF-kappaB: "
IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB dependent manner on human umbilical vein endothelial cells ( HUVEC )
"
ICOSL — NF-kappaB: "
IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB dependent manner on human umbilical vein endothelial cells ( HUVEC )
"
IL-1alpha — NF-kappaB: "
IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB dependent manner on human umbilical vein endothelial cells ( HUVEC )
"
CD8 → ICOSL: "
ICOSL blockade reduced CD8 ( + ) T cell proliferation by 70 % along with a marked decrease of IL-2 and IFN-gamma production in co-cultures with HUVEC
"
CD8 ⊣ ICOSL: "
Our data indicate a distinct role for ICOSL in EC-mediated CD8 ( + ) T cell costimulation with implications for human cardiac allograft rejection
"
Manually curated Databases
No curated data.