CD8+ T cells infiltrating into bile ducts in biliary atresia do not appear to function as cytotoxic T cells: a clinicopathological analysis

Abstract

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 situ distribution 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.

Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

“…For example, CD4 + and CD8 + T cells populate affected livers and are associated with the overexpression of activation markers, such as IFN-γ, IL-2, the IL-2 receptor CD25, TNF and the transferrin receptor CD71. 102–106 Cholangiocyte py knosis and necrosis have been associated with infiltration of mononuclear cells in the walls of interlobular bile ducts, duct walls at the porta hepatis and remnants of extra-hepatic bile ducts. 107–109 In vitro studies using T cells show that patients with biliary atresia have oligoclonal expansion of CD4 + and CD8 + T cells, 110 providing more direct evidence that tissue lymphocytes share common biological programmes.…”

Update on investigations pertaining to the pathogenesis of biliary atresia

“…This study strengthened the contention that the immune response, and not the initial viral infection, was responsible for the progression of bile duct injury. In human BA, the predominant cellular immune response at diagnosis encompasses activated CD4+ and CD8+ T cells within portal tracts that produce Th1 cytokines (IL-2, IFN-γ) and macrophages that generate TNF-α [61, 62, 73, 74]. These lymphocytes have been found invading between bile duct epithelia, leading to degeneration of intrahepatic bile ducts [75].…”

Aetiology of biliary atresia: what is actually known?

“…The cell lines appear to be oligoclonal at least in the CD4 + and CD8 + subsets identified by Mack et al [45]. Alternatively, Shinkai et al observed a predominantly CD8 + infiltrate in their infants with BA [46,47] though their study group was much smaller; and previous work has suggested poor CD8 + cytotoxic function [48]. Muraji et al has also described significantly more CD8+ T cells in the livers of BA infants, and interestingly, these appear to be of maternal origin [49].…”