Antiviral CD8⁺ T cell effector activities in situ are regulated by target cell type

Matthew M. Hufford, et al. 2010. J. Exp. Med. 208:167-180

Speaker: Ting-Jing Shen (沈庭靚)                                 Time: 14:10~15:00, Mar, 02, 2011

Commentator: Dr. Chrong-Reen Wang (王崇任 老師)       Place: Room 601

Abstract:

        CD8⁺ T cells play an important role in host responses against viral infections through directly lysing virus-infected cells and producing pro-inflammatory cytokines¹. Previous studies suggested that pro-inflammatory cytokines produced by CD8⁺ T cells that function to reduce viral infections may also promote pulmonary inflammation in severe influenza virus infection². Thus, it is important to determine the factors controlling the antiviral activities of CD8⁺ T cells in situ. Of influenza virus-infected lung, effector CD8⁺ T cells infiltrating into the pulmonary interstitium but not into the airspace were the major IFN-g-producing cells. Interestingly, the antiviral responses of effector CD8⁺ T cells were dependent on the target cell type encountered. CD45⁺ cells, predominately the CD11c^hi inflammatory mononuclear cells, served as the dominant antigen-presenting-cells to pulmonary interstitium-restricted CD8⁺ T cells. These CD45⁺CD11c^hi cells not only activated the cytolytic activity of effector CD8⁺ T cells but also induced the IFN-g production of effector CD8⁺ T cells through providing co-stimulating ligands, CD80 and CD86. In contrast, CD45^- influenza-infected epithelial cells only triggered the cytolytic activity of effector CD8⁺ T cells through perforin- and Fas-dependent elimination of infected cells in vivo. In conclusion, of the antiviral activities of effector CD8⁺ T cells, both CD45⁺ and CD45^- cells induced cytolytic activity whereas only CD45⁺ cells contributed to the IFN-g production. This study points out a novel view that the antiviral activities of effector CD8⁺ T cells could be modulated by target cells and provides a potential therapy for severe influenza infection by regulating the interaction of effector CD8⁺ T cells and its target cells to reduce the overt immune responses without affecting the viral clearance.

References:

1.      Zuzana Staneková and Eva Varečková. 2010. Virol.J. Conserved epitopes of influenza A virus inducing protective immunity and their prospects for universal vaccine development. 7:351-364.

2.      La Gruta, N.L., et al. 2007. Immunol. Cell Biol. A question of self-preservation: immunopathology in influenza virus infection. 85:85-92.