Decrease in the prevalence of IL-4-producing CD4+ T cells in patients with advanced stage of primary biliary cirrhosis.

Abstract

To elucidate the precise immunological features in primary biliary cirrhosis (PBC), we examined the relative prevalence of CD4+ T cells in either symptomatic PBC (sPBC) or asymptomatic PBC patients (aPBC), and furthermore, these results were compared with their histological features. Cytokine synthesis of peripheral blood mononuclear cells obtained from 24 PBC patients (9 sPBC and 15 aPBC) were examined by intracellular staining method. The relative prevalence of three distinct CD4+ T cells, gamma-interferon (IFN-gamma)-producing cells (Th1), interleukin-4 (IL-4)-producing cells (Th2), and the cells producing both IL-4 and IFN-gamma (Th0), was analyzed by FACScan and compared with those of closely age-matched healthy and disease controls. The results demonstrated that although a significant difference was not observed in the prevalence of Th1 or Th0, a remarkable difference was observed in the prevalence of Th2 (1.2+/-0.7 in sPBC, 4.1+/-1.3 in healthy subjects, 4.1+/-2.1 in aPBC, 3.4+/-1.3 in chronic hepatitis C, and 3.6+/-2.3 in cirrhosis secondary to CH-C; p < 0.05 for sPBC vs all others). Histological examination of these patients showed that all aPBC patients belonged to relatively early stage (stage I-II) and 7 of 8 sPBC patients belonged to late stage (stage III-IV). Thus, our results suggest that, mainly as a result of the decline of Th2, a predominance of Th1 may exist in advanced stage PBC. The present results demonstrated that a slight elevation of Th1 prevalence, as well as a significant decline of Th2 prevalence, was observed in peripheral blood of advanced stage PBC.