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 multiplication1,2. Listeria monocytogenes is an intracellular pathogen that replicates inside mononuclear phagocytes and hepatocytes of mice1-4. Invasion from the phagosomal compartment into the cytoplasmic compartment is the principal mechanism of intracellular survival5. 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 microbes1,2,8. T cells are also responsible for the highly effective protection in vaccinated mice against secondary infections1,2. Although the role of alphabeta T cells has been demonstrated in these immune responses, that of gammadelta T cells is unclear2,9,10. Here we use mice that selectively lack either alphabeta or gammadelta T cells as a result of targeted germ-line mutations in their T-cell receptor genes11,12 to investigate the relative roles of these T-cell populations during experimental infection with L. monocytogenes. We find that in primary listeriosis, either alphabeta or gammadelta T cells are sufficient for early protection. Resistance to secondary infection is mediated mainly by alphabeta T cells but also involves gammadelta T cells. Thus alphabeta T-cell-deficient mice can be rendered partially resistant by vaccination, and gammadelta T cells are shown to be responsible for this protective effect. In infected gammadelta T-cell-deficient mice we noticed the appearance of unusual liver lesions, indicating that gammadelta T cells have a unique regulatory role in this bacterial infection.