Different roles of alpha beta and gamma delta T cells in immunity against an intracellular bacterial pathogen

Several bacterial pathogens of medical importance are able to persist and replicate inside host mononuclear phagocytes. Protective immunity depends on specific T lymphocytes that induce granulomatous lesions at the sites of bacterial multiplication. Listeria monocytogenes is an intracellular pathogen that replicates inside mononuclear phagocytes and hepatocytes of mice. Invasion from the phagosomal compartment into the cytoplasmic compartment is the principal mechanism of intracellular survival. Early in infection, resistance against L. monocytogenes is mediated by polymorphonuclear phagocytes which destroy infected liver cells, followed by natural killer cells which activate macrophages by means of interferon-gamma (refs 6, 7). A specific immune response by T cells then develops which leads to sterile eradication of the microbes. T cells are also responsible for the highly effective protection in vaccinated mice against secondary infections. Although the role of alpha beta T cells has been demonstrated in these immune responses, that of gamma delta T cells is unclear. Here we use mice that selectively lack either alpha beta or gamma delta T cells as a result of targeted germ-line mutations in their T-cell receptor genes to investigate the relative roles of these T-cell populations during experimental infection with L. monocytogenes. We find that in primary listeriosis, either alpha beta or gamma delta T cells are sufficient for early protection. Resistance to secondary infection is mediated mainly by alpha beta T cells but also involves gamma delta T cells. Thus alpha beta T-cell-deficient mice can be rendered partially resistant by vaccination, and gamma delta T cells are shown to be responsible for this protective effect. In infected gamma delta T-cell-deficient mice we noticed the appearance of unusual liver lesions, indicating that gamma delta T cells have a unique regulatory role in this bacterial infection.