Loss of CD28 Expression by Liver-Infiltrating T Cells Contributes to Pathogenesis of Primary Sclerosing Cholangitis

摘要: Background & Aims T-cell–mediated biliary injury is a feature of primary sclerosing cholangitis (PSC). We studied the roles CD28 - T cells in PSC and their regulation by vitamin D. Methods Peripheral liver-infiltrating mononuclear were isolated from blood or fresh liver tissue. analyzed numbers, phenotypes, functions, localization patterns cells, along with ability to activate epithelial cells. measured levels tumor necrosis factor (TNF)α tissues patients effects exposure active D (1,25[OH]2D3) on expression CD28. Results A significantly greater proportion CD4 + CD8 that infiltrated , compared control tissue (CD4 : 30.3% vs 2.5%, P 68.5% 31.9%, was higher than cirrhosis nonalcoholic steatohepatitis ( activated CD69 CD45RA C-C chemokine receptor (CCR)7 effector memory perforin granzyme B cytotoxic which express CD11a, CX3CR1, C-X3-C motif 6 (CXCR6), CCR10—consistent infiltration around bile ducts. Compared produced interferon γ TNFα Conclusions Inflammatory T cells accumulate livers localize The TNFα-rich microenvironment this promotes inflammation; these are reversed in vitro.