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T-cell–mediated biliary injury is a feature of primary sclerosing cholangitis (PSC). We studied the roles of CD28^- T cells in PSC and their regulation by vitamin D.

Peripheral and liver-infiltrating mononuclear cells were isolated from blood or fresh liver tissue. We analyzed numbers, phenotypes, functions, and localization patterns of CD28^- T cells, along with their ability to activate biliary epithelial cells. We measured levels of tumor necrosis factor (TNF)α in liver tissues from patients with PSC and the effects of exposure to active vitamin D (1,25[OH]2D3) on expression of CD28.

A significantly greater proportion of CD4⁺ and CD8⁺ T cells that infiltrated liver tissues of patients with PSC were CD28^-, compared with control liver tissue (CD4⁺: 30.3% vs 2.5%, P < .0001; and CD8⁺: 68.5% vs 31.9%, P < .05). The mean percentage of CD4⁺CD28^- T cells in liver tissues from patients with PSC …