Liver-resident CD44hiCD27- γδT Cells Help to Protect Against Listeria monocytogenes Infection

BACKGROUND & AIMS: Gamma delta (gamma delta) T cells are heterogeneous and functionally committed to producing interferon (IFN)-gamma and interleukin (IL)-17. gamma delta T cells are defined as tissue-resident lymphocytes in barrier tissues. Among them, IL-17-producing gamma delta T cells are relatively abundant in the liver. However, a systematic and comprehensive understanding of the residency characteristics and function of hepatic IL-17A(+) gamma delta T cells is lacking. METHODS: We undertook a single-cell analysis of gamma delta T17 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 liverresident CD44(hi)CD27(-) gamma delta T cells in Listeria monocytogenes infection. Transwell assay was used to assess the role of macrophages in the chemotaxis of liver-resident CD44(hi)CD27(-) gamma delta T cells. RESULTS: We identified hepatic IL-17A-producing gamma delta T cells as CD44(hi)CD27(-) gamma delta T cells. They had tissue-resident characteristics and resided principally within the liver. V gamma 6(+) T cells also exhibited liver-resident features. Liver-resident CD44(hi)CD27(-) gamma delta T cells had significantly increased proliferation capacity, and their proportion rapidly increased after infection. Some CD44(hi)CD27(-) gamma delta T cells could produce IL-17A and IFN-gamma simultaneously in response to Lm infection. Adoptive transfer of hepatic CD44(hi)CD27(-) gamma delta T cells into Lm-infected TCR delta(-/-) mice led to markedly lower bacterial numbers in the liver. Hepatic macrophages promoted the migration and accumulation of liver-resident CD44(hi)CD27(-) gamma delta T cells into infection sites. CONCLUSIONS: Liver-resident CD44(hi)CD27(-) gamma delta T cells protect against Lm infection. Hepatic macrophages coordinate with liver-resident CD44(hi)CD27(-) gamma delta T cells and contribute to the clearance of Lm at the early stage of infection corporately.