Innate immunity defines the capacity of antiviral T cells to limit persistent infection

Andrews, D.M., et al. 2010. J. Exp. Med. 207, 1333-1343

Speaker: Yu-Ting Liao (廖郁婷)                            Time: 14:10~15:00, Sep. 29, 2010

Commentator: Yao Chang (張堯老師)         Place: Room 601

Abstract:

Natural killer (NK) cells serve as an important role in innate immune responses against tumors and microbial pathogens. Since many of the NK-cell activating and inhibitory receptors and their ligands have been identified, a molecular basis for NK cell recognition of virus-infected cells such as murine cytomegalovirus infection was well understood¹. According to the previous studies, NK cells from C57BL6/J mice express Ly49H receptor, which initiates cell-mediated cytotoxicity, cytokine production and proliferation when Ly49H binds to MCMV-encoded glycoprotein m157 on their cell surface². However, the contribution and biological significance of NK cells to innate immunity and adaptive immunity are crucial topics to enunciate. In this study, the authors used Ly49H^- (BALB/c) mice and Ly49H⁺ (BABL.B6-CT8) mice to evaluate the interaction between NK-cell mediated activity and antiviral cytotoxic T lymphocyte (CTL) responses and found that the CTL response was significantly reduced in Ly49H⁺ mice compared with Ly49H^- mice at day 8 and day 10 after MCMV infection. The NK cell depletion of Ly49H⁺ mice showed antiviral CTL function were similar to that measured in Ly49H^- mice at day 10 post infection. Moreover, NK cell activation in Ly49H⁺ mice affect antiviral CD4 and CD8 T cell responses. To define relevant mechanisms, the results showed that the number of infected FDG⁺CD11c⁺MHCII⁺ DCs/APCs were decreased in Ly49H⁺ mice but not observed in Ly49H⁺ mice depleted of NK cells. In BALB.B6-Cmv1r.pfp^-/- mice, they demonstrated that the perforin-dependent elimination of infected DCs/APCs may be involved. The different frequency and number of infected DCs/APCs affect antiviral T cell responses in the presence of NK-cell mediated responses. Furthermore, NK cells regulate T cell function that limit viral persistence differs in Ly49H^- and Ly49H⁺ mice. The numbers of CD8⁺IE1⁺ and CD4⁺IFN-γ⁺ T cell in salivary gland in Ly49H^- mice were higher than in Ly49H⁺ mice. The depletion of CD4⁺ or CD8⁺ T cells proved that different CD4⁺ T cell responses resulted in limiting viral replication. Collectively, their results proved that the NK cells influence the extent of

DC/APC infection and the capacity of antiviral T cells in MCMV infection.

References:

1.      Hamerman, J.A., et al. 2005. NK cells in innate immunity. Curr. Opin. Immunol. 17, 29-35.

2.      Lanier, L.L. 2008. Evolutionary struggles between NK cells and viruses. Nat. Rev. Immunol. 8, 259-268.