Liver-resident CD44CD27 γδT Cells Help to Protect Against Listeria monocytogenes Infection.

Background & Aims: Gamma delta (γδ) T cells are heterogeneous and functionally committed to producing interferon (IFN)-γ and interleukin (IL)-17. γδT cells are defined as tissue-resident lymphocytes in barrier tissues. Among them, IL-17-producing γδT cells are relatively abundant in the liver. However, a systematic and comprehensive understanding of the residency characteristics and function of hepatic IL-17A γδT cells is lacking.

Methods: We undertook a single-cell analysis of γδT17 cells derived from murine livers. A parabiosis model was used to assess tissue residency. Fluorescence-activated cell sorting and adoptive transfer experiments were used to investigate the response and protective role of liver-resident CD44CD27 γδT cells in Listeria monocytogenes infection. Transwell assay was used to assess the role of macrophages in the chemotaxis of liver-resident CD44CD27 γδT cells.

Results: We identified hepatic IL-17A-producing γδT cells as CD44CD27 γδT cells. They had tissue-resident characteristics and resided principally within the liver. Vγ6 T cells also exhibited liver-resident features. Liver-resident CD44CD27 γδT cells had significantly increased proliferation capacity, and their proportion rapidly increased after infection. Some CD44CD27 γδT cells could produce IL-17A and IFN-γ simultaneously in response to Lm infection. Adoptive transfer of hepatic CD44CD27 γδT cells into Lm-infected TCRδ mice led to markedly lower bacterial numbers in the liver. Hepatic macrophages promoted the migration and accumulation of liver-resident CD44CD27 γδT cells into infection sites.

Conclusions: Liver-resident CD44CD27 γδT cells protect against Lm infection. Hepatic macrophages coordinate with liver-resident CD44CD27 γδT cells and contribute to the clearance of Lm at the early stage of infection corporately.