Source Infection & Immunity Program, Singapore Institute for Clinical Sciences, A*STAR, Singapore.
BACKGROUND AND AIMS: During viral infection, the activities of virus-specific CD8T cells are carefully regulated to prevent severe damage of the infected organs. We investigated the mechanisms that control the functions of activated T cells.
METHODS: We measured size of the population of activated and proliferating CD8T cells population and the functional pattern of CD8T cells specific for the whole Hepatitis B virus proteome and for selected heterologous virus (Epstein-Barr virus, human cytomegalovirus and influenza virus) specificities in blood samples from 18 patients with acute hepatitis B. We analyzed the effects of different modulatory mechanisms, such as inhibitory molecules, suppressive cytokines (interleukin-10) and arginase on the activities of CD8T cells.
RESULTS: In patients with acute hepatitis B, the expansion of activated and proliferating (HLA-DR/CD38+, Ki-67+/Bcl-2 (low)) CD8T cells did not quantitatively match their specific functions ex vivo; virus-specific CD8T cells had functional impairments that were temporally restricted to the acute phase of viral hepatitis. These impairments in function were not limited to HBV-specific CD8+ T cells, were also observed in CD8T cells with specificities for other viruses. We investigated possible causes of antigen-independent CD8T cell inhibition and found that the increased levels of arginase observed in patients with acute hepatitis could suppress the function of activated, but not resting, CD8T cells.
CONCLUSION: The increased level of arginase in patients with acute hepatitis B suppresses the functions of activated CD8T cells. This mechanism might limit the amount of liver damage caused by activated CD8T cells in patients with acute HBV infection.