Interferon-gamma plays a nonredundant role in mediating T cell-dependent outward vascular remodeling of allogeneic human coronary arteries.
Vascular remodeling (change in vessel diameter) rather than intimal hyperplasia is the most important predictor of luminal loss in immune-mediated arterial injury, yet little is known about its mechanisms. Here, we show that outward vascular remodeling and intimal thickening, two manifestations of arteriosclerosis with opposing effects on luminal size, result from immune effector mechanisms that are T-cell dependent and interferon (IFN)-gamma mediated. In our in vivo model of human coronary artery injury by allogeneic peripheral blood mononuclear cells, both processes occur concurrently and are characterized by T-cell infiltrates with a predominantly IFN-gamma-producing cytokine profile. Neutralization of IFN-gamma inhibits the arterial and intimal expansion, whereas administration of IFN-gamma enhances these effects. The nonredundant role of IFN-gamma in T-cell-dependent remodeling of human coronary arteries demonstrated here presents a new therapeutic target for preservation of vessel lumen in arteriosclerosis.
Wang
Yinong
Y
Interdepartmental Program in Vascular Biology and Transplantation, and the Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Burns
William R
WR
Tang
Paul C Y
PC
Yi
Tai
T
Schechner
Jeffrey S
JS
Zerwes
Hans-Guenter
HG
Sessa
William C
WC
Lorber
Marc I
MI
Pober
Jordan S
JS
Tellides
George
G
D019264:Adoptive Transfer; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D003331:Coronary Vessels / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous; D017539:Tunica Intima / Q000473:pathology
D011994:Recombinant Proteins; D007371:Interferon-gamma