| |
Second
Department of Internal Medicine (FK, YT, FM), Tokyo Medical and Dental University,
and Department of Health Science (CS), Faculty of Medicine, Tokyo Medical
and Dental University, Tokyo, Japan |
| |
SUMMARY: Inflammation of the portal and periportal areas is a common
feature of chronic hepatitis C. Antigen-presenting dendritic cells are
located in the portal area, and infiltrating T cells are initially exposed
to infected hepatocytes in the periportal area. Thus, these areas could
be sites of the initial processes of the immune response in chronic hepatitis
C. C-C chemokines (dendritic-cell-derived C-C chemokine [DC-CK1] and regulated
upon activation, normal T-cell expressed and secreted [RANTES])-attracting
T cells may play a role in the portal inflammatory changes. The relationship
between the expression of these C-C chemokines, which attract T cells
and the infiltration of T cells into the liver of patients with chronic
hepatitis C, was examined by in situ hybridization and reverse transcription-polymerase
chain reaction. T-cell activation was examined by immunostaining T-cell
subsets. Specific signals were detected for DC-CK1 mRNA in mononuclear
cells mainly in the portal area and for RANTES mRNA in the portal area
and at sites of piecemeal necrosis in the liver of patients with chronic
hepatitis C. Naive T cells were located mainly in the portal area, whereas
active T cells were found mainly at sites of piecemeal necrosis in the
periportal area. In addition, hepatic DC-CK1- and RANTES-mRNA levels were
significantly correlated with serum alanine aminotransferase levels (p
> 0.001). These results suggest that the local production of DC-CK1
and RANTES participates in immune responses by attracting naive and active
T cells to the portal and periportal areas, respectively. (Lab Invest
2000, 80: 279-289)
|
