| Autor: |
Crotta, Stefania, Stilla, Annalisa, Wack, Andreas, D'Andrea, Annalisa, Nuti, Sandra, D'Oro, Ugo, Mosca, Marta, Filliponi, Franco, Brunetto, R. Maurizia, Bonino, Ferruccio, Abrignani, Sergio, Valiante, Nicholas M. |
| Zdroj: |
The Journal of Experimental Medicine; January 2002, Vol. 195 Issue: 1 p35-42, 8p |
| Abstrakt: |
The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in ∼170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection. |
| Databáze: |
Supplemental Index |
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