?d T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection

Dong, Peng; Ju, Xiangwu; Yan, Yiwu; Zhang, Siya; Cai, Menghua; Wang, Huaishan; Chen, Hui; Hu, Yu; Cui, Lianxian; Zhang, Jianmin; He, Wei

γδ T cells in PBMCs could be activated by influenza virus (H1N1, H2N2, and H3N2) infection (17) ; however, the interplay between the HPAI H5N1 virus and γδ T cells has not been reported. In our study, we demonstrate for the first time that the HPAI H5N1 virus could directly induce severe γδ T cell agglutination and activation in vitro. The expression of CD69 and the secretion levels of the cytokines GM-CSF, IFN-γ, TNFα, IL-4, and IL-5 in γδ T cells were markedly increased after HPAI H5N1 infection. Therefore, γδ T cells could participate in viral clearance directly by the production of IFN-γ and indirectly through the regulation of other immune effector cells by the production of immunomodulatory cytokines. Moreover, the ability of the HPAI H5N1 virus to activate γδ T cells was higher than that of H1N1; this result is consistent with the in vivo virulence of these strains. H5N1 has been reported to infect many types of immune cells, including dendritic cells (DCs), monocytes, macrophages, neutrophils, natural killer (NK) cells, and B cells (30) (31) (32) (33) . Nevertheless, our study confirms that γδ T cells are resistant to HPAI H5N1 infection, consistent with previous reports showing that γδ T cells were not susceptible to influenza A virus infection (34, 35) . Therefore, we speculate that the rapid activation response and ability to resist HPAI H5N1 infection increase the advantage of γδ T cells in controlling viral infection compared with that of other immune cells.