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De novoformation of lymphoid tissue is one of the characteristic features of chronic inflammation. The formation of T cell–mature dendritic cell (DC) clusters has been previously demonstrated in chronically inflamed skin infected with Candida albicans. A functional similarity was also found between chronic inflammation and the T‐cell zone of lymph nodes (LNs), since a substantial fraction of phenotypically mature DCs in both tissues expressed CCL22 (macrophage‐derived chemokine; MDC) and were closely surrounded by memory‐type T cells expressing its receptor, CCR4. To analyse the nature of T cell–mature DC interactions further in chronically inflamed skin and LNs, the present study focuses on another chemokine system, namely CCL19 (EBI1 ligand chemokine; ELC), CCL21 (secondary lymphoid tissue chemokine; SLC) and their shared receptor, CCR7. RT‐PCR analysis revealed expression of CCL19, CCL21, and CCR7 at high levels in LNs and at low levels in inflamed skin. Using immunohistochemistry, the majority of DC‐Lamp+mature DCs in the T‐cell area of LNs expressed CCL19 and were surrounded by CCR7+naïve‐type lymphocytes, while CCL21 was expressed in reticular stromal cells and vascular endothelial cells. Very few mature DCs in LNs were found to express CCR7. In contrast, the majority of DC‐Lamp+mature DCs in inflamed skin were totally negative for CCL19 and were surrounded by CCR7−memory‐type T cells. Furthermore, CCL21 expression in the inflamed skin was detected in dermal lymphatic endothelial cells and rare CCR7+mature DCs were mostly seen within the lymphatic vessels. In normal skin, on the other hand, no cells immunoreactive for CCL19, CCL21, or CCR7 were found. The present study thus reveals a striking difference in the function of mature DCs between LNs and chronically inflamed skin. Copyright © 2002 John Wiley & Sons, Ltd.

It is speculated that immune mechanisms are involved in bile duct damage in biliary atresia (BA), as in primary biliary cirrhosis (PBC). In BA, however, no reports have described the in situdistribution of cytotoxic T lymphocytes (CTLs) using specific markers, nor has the clinical association been clarified. The present study describes the immunohistochemical distribution of CD8+T cells and the relevant markers [perforin, granzyme B, FasL (CD95L)] in 47 cases of BA operated upon at days 12–79. The results were compared with those of PBC. In BA, CD8+T cells infiltrated bile ducts in a way similar to that observed in PBC. However, in sharp contrast to PBC, none of the inflammatory cells infiltrating into the bile ducts in BA expressed cytotoxic markers such as perforin, granzyme B, or Fas ligand (FasL). Clinical follow‐up of patients with BA revealed that a greater degree of infiltration of bile ducts by CD8+T cells is associated with better liver function. Taken together, these data suggest the absence of direct CTL activity against bile ducts in BA in the postnatal period. Copyright © 2000 John Wiley & Sons, Ltd.

Progressive fibrosis, despite successful surgical treatment, is one of the serious complications of biliary atresia. To understand the mechanism of this fibrosis, the in situexpression of fibrogenic growth factors (TGF‐β and PDGF) and their corresponding receptors was studied by immunohistochemistry using frozen sections. The results were compared between the early (n=12) and late (n=6) stages. The early stage was characterized by abundant expression of all ligands and receptors, together with type I procollagen (PC‐I). The major cellular sources were activated fibroblasts/myofibroblasts distributed mostly in the portal tracts. Macrophages also expressed all the ligands and the receptors, but to a lesser degree. Bile duct cells strongly expressed TGF‐β RI and RII and PDGF AA and BB, but focally expressed TGF‐β. All of these decreased in the late stage of biliary atresia. These results suggest that TGF‐β and PDGF play important roles in the fibrogenesis of biliary atresia, especially in its early stage, acting either by autocrine or paracrine mechanisms involving activated fibroblasts/myofibroblasts, bile duct cells, and macrophages. Copyright © 2000 John Wiley & Sons, Ltd.