TIPE2 protein negatively regulates HBV-specific CD8(+) T lymphocyte functions in humans

摘要

Cytotoxic T cell-mediated killing of virus-infected hepatocytes is an important pathogenic process of hepatitis B. However, its underlying molecular mechanisms are not fully understood. TNFAIP8L2 (TIPE2) is a newly described anti-inflammatory protein that is essential for maintaining immune homeostasis. In this study, we found that the protein levels of TIPE2 in PBMCs of hepatitis B patients were significantly reduced and negatively correlated with the sera values of aminotransferases. Importantly, TIPE2 protein was downregulated preferentially in cytotoxic CD8(+) T cells, not CD4(+) helper T cells. The CD8(+) T cells with low TIPE2 expression were more activated and produced higher levels of perforin, granzyme B, and IFN-gamma. As a result, their cytolytic activity was markedly enhanced. Interestingly, HBc(18-27) peptide stimulation could reduce TIPE2 expression in PBMCs. These results indicate that TIPE2 plays an important role in regulating HBV-specific CD8(+) T cell functions in patients with hepatitis B. (C) 2014 Elsevier Ltd. All rights reserved.