Immune protection and control of inflammatory tissuenecrosis by γδ T cells

Host defenses against experimental listeriosis in mice involve neutrophils, macrophages, NK cells, and αβ T cells. Recently γδ cells have also been implicated in antilisterial resistance. However, their specific role has remained unclear. Here we show that efficient resistance to infection by this bacterium depends on the functions of both αβ and γδ cells in both primary and secondary responses. We also present evidence that these functions are complementary. In the livers of αβ T cell-depleted mice, bacteria grow to large numbers within hepatocytes but are infrequently found extracellularly. Granulomatous lesions are more frequent and somewhat larger than in normal controls, but remain focal. Neutrophils are absent from liver lesions in these mice. In contrast, the livers of γδ T cell-depleted mice contain many extracellular bacteria, but do not show hepatocytes containing large numbers of Listeria. Liver lesions in γδ cell-depleted mice are far more extensive than in normal controls or in αβ cell-depleted mice, and contain large numbers of neutrophils. Particularly in secondary listeriosis, γδ T cell-depleted mice show vast coalescent areas of necrotic liver parenchyma within 48 h after infection. Because the bacterial numbers in γδ cell-depleted mice remain lower than in γδ cell-depleted mice, increased mortality in the former may be in part caused by liver failure. We conclude that γδ cells are required to control inflammatory reactivity and to prevent excessive liver damage during the immune response to Listeria monocytogenes.