Background— CD4-positive lymphocytes, the major T-cell population in human atheroma, mainly secrete Th-1-type proinflammatory cytokines, like interferon (IFN)γ, tumor necrosis factor (TNF)α, and interleukin (IL)-2, thus promoting atherogenesis. Recent data suggest that the nuclear transcription factors liver X receptor-alpha and liver X receptor-beta (LXRα and LXRβ) limit plaque formation in animal models by modulating macrophage function. Still, the role of LXRs in CD4-positive lymphocytes is currently unexplored.

Methods and Results— Human CD4-positive lymphocytes express LXRα and LXRβ mRNA and protein. Activation of CD4-positive cells by anti-CD3 mAbs, anti-CD3/CD28 mAbs, as well as PMA/ionomycin significantly increased Th1-cytokine mRNA and protein expression. Treatment with the LXR activator T0901317 reduced this increase of IFNγ, TNFα, and IL-2 in a concentration-dependent manner with a maximum at 1 μmol/L T0901317. Transient transfection assays revealed an inhibition of IFNγ promoter activity by T0901317 as the underlying molecular mechanism. Such anti-inflammatory actions were also evident in cell–cell interactions with medium conditioned by T0901317-treated CD4-positive cells attenuating human monocyte CD64 expression.

Conclusions— Human CD4-positive lymphocytes express both LXRα and LXRβ, and LXR activation can reduce Th-1 cytokine expression in these cells. These data provide new insight how LXR activators might modulate the inflammatory process in atherogenesis and as such influence lesion development.