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.