Immunopathogenesis of primary biliary cirrhosis: an old wives' tale

Immunity & Ageing

Table 1 Features of immunological ageing seen in the cellular pathology of primary biliary cirrhosis (PBC).

Ageing Feature	Presence in PBC
Decreased regulatory T cell (Treg) response	- Increased CD127 and decreased CD39 on CD8+ T cells
	-CD8+CD28- cells fail to display a regulatory response when incubated with IL-10
Decreased telomere length	-Quantitative fluorescence in situ hybridisation has shown decreased telomere length in biliary epithelial cells (BEC) of primary biliary cirrhosis (PBC) patients
DNA damage	- gammaH2AX-DNA-damage-foci detected in BEC
Increased apoptosis	-Apoptotic marker Bcl-2 in BEC (may increase PDC-E2 exposure)
	-Increased apoptotic marker CD95 (Fas) on BEC
	-Unmodified PDC-E2 found in apoptotic blebs (apotopes) in BEC
Increased cellular senescence	-Increased expression of senescence markers p16 and p21 in BEC
	-Decreased Ki67 expression in BEC, indicating decreased cellular proliferation
	-Decreased Bmi-1 (senescence regulator) expression in BEC
Increased autophagy	-Increased LC3 expression in BEC, which correlated with increased autophagy

Several features characterise an aged immune system, including changes in T cell response, decreased telomere length and DNA damage, as well as apoptosis and cellular senescence. These features have also been demonstrated in liver tissues from patients with PBC. These findings may, in part, explain why PBC patients often present in middle age, compared to other autoimmune diseases. Please see relevant sections in the text for more detailed descriptions.

ISSN: 1742-4933