Distribution of non‐lymphoid, inflammatory cells in chronic HBV infection

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Abstract
Non‐lymphoid cells play a key role in the initiation and maintenance of cellular immune responses. Usingin‐situimmunohistochemical techniques and a panel of monoclonal antibodies (mcabs) reactive with B5‐fixed, paraffin‐embedded liver biopsies, we analysed the non‐lymphoid cell component in inflammatory infiltrates in 20 cases of chronic hepatitis B virus (HBV) infection. In addition, lymphocyte subsets and HLA‐DR antigens were studiedMcab KP1 labelled scattered Kupffer cells, which variably expressed HLA‐DR antigens. Their random distribution and lack or significant topographical association with lymphocytes suggest that classical Kupffer cells do not play a major role in cell‐mediated immune reactions. On the other hand, mcab Mac387 was unreactive with normal liver tissue but labelled HLA‐DR+ dendritic cells in areas of intralobular inflammation. On (immuno)electron microscopy, these Mac387 + dendritic cells were situated in the Disse space, where they formed close contacts with lymphocytes. Similar dendritic cells were situated at the edge of portal tracts in cases of chronic active, but not chronic persistent hepatitis. Immunostaining on serial frozen sections revealed their close topographical association with cytotoxic/suppressor T‐cells, suggesting that Mac387 + HLA‐DR + dendritic cells play an immunomodulatory role in the effector arm of the cellular immune response that takes place in the periphery of portal tracts and the lobular parenchyma, and that involves activation and proliferation of cytotoxic T cells.Finally, large Mac387 – HLA‐DR + dendritic cells expressing the LN2 marker were situated amidst helper/inducer T‐cells in the centre of severely inflamed portal tracts. In analogy with their role in the lymph node, these cells are likely to act as accessory cells in the afferent arm of the immune response that involves antigen presentation to helper T‐cells which subsequently assist in the generation of plasma cells.According to the types of dendritic cells and their associated T‐cell subsets, different functional domains involved in the afferent and efferent limbs of the immune response can be distinguished in liver tissue involved by chronic HBV infection.