Objectives--T-lymphocytes and interferon- (IFN-) contribute to leukocyte recruitment in postcapillary venules during hypercholesterolemia. Our objectives were to determine whether: (1) T-lymphocytes are the source of this IFN-, and (2) whether T-cell-derived IFN- also mediates the accompanying arteriolar dysfunction and platelet adhesion.

Methods and Results--Intravital videomicroscopy was used to quantify arteriolar responses to acetylcholine, and leukocyte and platelet adhesion in postcapillary venules of wild-type (WT), immunodeficient (SCID), and IFN-^-/- mice on a normal (ND) or high-cholesterol (HC) diet. Acetylcholine-induced arteriolar dilation was impaired in WT-HC, compared with WT-ND. This endothelial dysfunction was absent in SCID-HC or IFN-^-/--HC mice. Vasodilation was impaired by transfer of WT, but not IFN-^-/-, T-cells to these immunodeficient mice. WT-HC mice exhibited elevated leukocyte and platelet adhesion in venules, versus WT-ND. This blood cell recruitment was attenuated to ND levels in SCID-HC and IFN-^-/--HC mice, but restored to WT-HC levels by transfer of WT, but not IFN-^-/-, T-lymphocytes.

Conclusions--These data reveal a novel role of T-lymphocyte-derived IFN- in the development of endothelial dysfunction in arterioles during hypercholesterolemia and extend our previous observations that IFN- mediates both inflammatory and thrombogenic responses to hypercholesterolemia in postcapillary venules.