?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

Sialic acid receptors are usually attached to the terminal galactose of cell surface glycoproteins by α-2,3 or α-2,6 linkages. TCR γδ and NKG2D, which play critical roles in antigen recognition and γδ T cell activation, are the two most important glycoprotein receptors on the surface of γδ T cells. We initially examined the relative contribution of TCR γδ and NKG2D in rHA-induced γδ T cell activation. However, in our study, treating γδ T cells with anti-TCR γδ and anti-NKG2D mAbs could not inhibit HA trimer-induced γδ T cell activation. Nevertheless, our result cannot totally rule out the participation of TCR γδ and NKG2D in HA-induced activation, because the mAbs may not completely block the HA binding sites. Therefore, the specific glycoprotein receptors mediating the binding of HA to γδ T cells need further study. To determine the signaling pathways involved in the HA trimer-induced activation of γδ T cells, we treated HA trimer-stimulated γδ T cells with the PI3-K inhibitors wortmannin or Ly294002 and with the immunosuppressive drug CsA. We found that HA trimer-induced γδ T cell activation was inhibited by CsA but not by wortmannin or LY294002. CsA is a phosphatase calcineurin inhibitor that affects a subset of calciumassociated signaling events similar to those involved in T cell activation (40) . The inhibitory effect of CsA was also consistent with our discovery that HA trimers could induce an increase in the intracellular free calcium concentration upon γδ T cell activation.