Different roles of αβ and γδ T cells in immunity against an intracellular bacterial pathogen

Abstract

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^1,2. Listeria monocytogenes is an intracellular pathogen that replicates inside mononuclear phagocytes and hepatocytes of mice^1–4. Invasion from the phagosomal compartment into the cytoplasmic compartment is the principal mechanism of intracellular survival⁵. Early in infec-tion, resistance against L. monocytogenes is mediated by polymor-phonuclear phagocytes which destroy infected liver cells, followed by natural killer cells which activate macrophages by means of interferon-γ (refs 6, 7). A specific immune response by T cells then develops which leads to sterile eradication of the microbes^1,2,8. T cells are also responsible for the highly effective protection in vaccinated mice against secondary infections^1,2. Although the role of αβ T cells has been demonstrated in these immune responses, that of γδ T cells is unclear^2,9,10. Here we use mice that selectively lack either αβ or γδ T cells as a result of targeted germ-line mutations in their T-cell receptor genes^11,12 to investigate the relative roles of these T-cell populations during experimental infection with L. monocytogenes. We find that in primary listeriosis, either αβ or γδ T cells are sufficient for early protection. Resistance to second-ary infection is mediated mainly by αβ T cells but also involves γδd T cells. Thus αβ T-cell-deficient mice can be rendered partially resistant by vaccination, and γδ T cells are shown to be responsible for this protective effect. In infected γδ T-cell-deficient mice we noticed the appearance of unusual liver lesions, indicating that γδ T cells have a unique regulatory role in this bacterial infection.