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

P Mombaerts, J Arnoldi, F Russ, S Tonegawa… - Nature, 1993 - nature.com
P Mombaerts, J Arnoldi, F Russ, S Tonegawa, SHE Kaufmann
Nature, 1993nature.com
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 infec …
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 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 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 microbes1,2,8. T cells are also responsible for the highly effective protection in vaccinated mice against secondary infections1,2. Although the role of αβ T cells has been demonstrated in these immune responses, that of γδ T cells is unclear2,9,10. 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 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 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.
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