Antigen-independent activation of resting T-cells in the liver of patients with chronic hepatitis

Abstract

Since the adult liver is an organ without constitutive lymphoid components, any intra-hepatic T cell found in chronic viral hepatitis should have compartmentalised to the liver after infection and inflammation. In liver biopsies from patients with chronic hepatitis C there is a great discrepancy between the percentage of activated T cells and the frequency of antigen-specific T cells. Usually, 40 to 80% of the liver-infiltrating T cells express activation markers, whereas only 0.5%, at best, of these cells are specific for any HCV protein. This finding suggests that there may be antigen independent mechanisms activating bystander T cells. We investigated whether human resting T cells could be activated to proliferate and display effector function in the absence of TcR occupancy. We have found that a combination of IL-2, TNF alpha and IL-6 could activate highly purified naive and memory T cells to proliferate. Under these conditions, resting memory T cells could also display effector function, as assessed by cytokine synthesis and help for IgG production by B cells. This novel antigen-independent pathway of T cell activation may play an important role in vivo in activating effector T cells in the liver and in maintaining the clonal size of peripheral memory T cells in the absence of antigenic stimulation.