Regulation of T cell function by microRNA-720.

Published

Journal Article

Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic HBV infection (CHB). However, the ongoing anti-HBV CD8(+) T cell responses in the lymphoid organs are largely unknown due to the infeasibility of obtaining lymphoid organs from CHB patients. Here we demonstrate that the percentage of HBV-specific CD8(+) T cells is higher in the spleen of CHB patients than that from peripheral blood and liver. Although they do respond to TCR stimulation and produce IFNγ, the cells proliferate poorly. Furthermore, miR-720 expression is upregulated in HBV-specific CD8(+) T cells. Overexpression of miR-720 in primary human CD8(+) T cells inhibits TCR stimulation-induced proliferation. We also demonstrate that TGFβ sustains miR-720 upregulation after TCR stimulation, and blood TGFβ levels are associated with the outcome of type I interferon treatment of CHB patients. Thus, therapies targeting miR-720 may help restore impaired immunity in CHB patients.

Full Text

Duke Authors

Cited Authors

  • Wang, Y; Zhang, Z; Ji, D; Chen, G-F; Feng, X; Gong, L-L; Guo, J; Li, Z-W; Chen, C-F; Zhao, B-B; Li, Z-G; Li, Q-J; Yan, H-P; Sempowski, G; Wang, F-S; He, Y-W

Published Date

  • July 22, 2015

Published In

Volume / Issue

  • 5 /

Start / End Page

  • 12159 -

PubMed ID

  • 26199080

Pubmed Central ID

  • 26199080

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

International Standard Serial Number (ISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/srep12159

Language

  • eng