IMMUNE PROTECTION AND CONTROL OF INFLAMMATORY TISSUE NECROSIS BY GAMMA-DELTA T-CELLS

Host defenses against experimental listeriosis in mice involve neutrop hils, macrophages, NK cells, and alpha beta T cells. Recently gamma de lta T cells have also been implicated in antilisterial resistance. How ever, their specific role has remained unclear. Here we show that effi cient resistance to infection by this bacterium depends on the functio ns of both alpha beta and gamma delta T cells in both primary and seco ndary responses. We also present evidence that these functions are com plementary. In the livers of alpha beta T cell-depleted mice, bacteria grow to large numbers within hepatocytes but are infrequently found e xtracellularly. Granulomatous lesions are more frequent and somewhat l arger than in normal controls, but remain focal. Neutrophils are absen t from liver lesions in these mice. In contrast, the livers of gamma d elta T cell-depleted mice contain many extracellular bacteria, but do not show hepatocytes containing large numbers of Listeria. Liver lesio ns in gamma delta T cell-depleted mice are far more extensive than in normal controls or in alpha beta T cell-depleted mice, and contain lar ge numbers of neutrophils. Particularly in secondary listeriosis, gamm a delta T cell-depleted mice show vast coalescent areas of necrotic li ver parenchyma within 48 h after infection. Because the bacterial numb ers in gamma delta T cell-depleted mice remain lower than in alpha bet a T cell-depleted mice, increased mortality in the former may be in pa rt caused by liver failure. We conclude that gamma delta T cells are r equired to control inflammatory reactivity and to prevent excessive li ver damage during the immune response to Listeria monocytogenes.