Murine CXCR3CXCR6γδT Cells Reside in the Liver and Provide Protection Against HBV Infection.

Gamma delta (γδ) T cells play a key role in the innate immune response and serve as the first line of defense against infection and tumors. These cells are defined as tissue-resident lymphocytes in skin, lung, and intestinal mucosa. They are also relatively abundant in the liver; however, little is known about the residency of hepatic γδT cells. By comparing the phenotype of murine γδT cells in liver, spleen, thymus, and small intestine, a CXCR3CXCR6 γδT-cell subset with tissue-resident characteristics was found in liver tissue from embryos through adults. Liver sinusoidal endothelial cells mediated retention of CXCR3CXCR6 γδT cells through the interactions between CXCR3 and CXCR6 and their chemokines. During acute HBV infection, CXCR3CXCR6 γδT cells produced high levels of IFN-γ and adoptive transfer of CXCR3CXCR6 γδT cells into acute HBV-infected TCRδ mice leading to lower HBsAg and HBeAg expression. It is suggested that liver resident CXCR3CXCR6 γδT cells play a protective role during acute HBV infection. Strategies aimed at expanding and activating liver resident CXCR3CXCR6 γδT cells both or have great prospects for use in immunotherapy that specifically targets acute HBV infection.