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CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity

Author

Listed:
  • Yasmine Belkaid

    (National Institutes of Health
    Children's Hospital)

  • Ciriaco A. Piccirillo

    (National Institutes of Health)

  • Susana Mendez

    (National Institutes of Health)

  • Ethan M. Shevach

    (National Institutes of Health)

  • David L. Sacks

    (National Institutes of Health)

Abstract

The long-term persistence of pathogens in a host that is also able to maintain strong resistance to reinfection, referred to as concomitant immunity, is a hallmark of certain infectious diseases, including tuberculosis and leishmaniasis. The ability of pathogens to establish latency in immune individuals often has severe consequences for disease reactivation1,2,3. Here we show that the persistence of Leishmania major in the skin after healing in resistant C57BL/6 mice is controlled by an endogenous population of CD4+CD25+ regulatory T cells. These cells constitute 5–10% of peripheral CD4+ T cells in naive mice and humans, and suppress several potentially pathogenic responses in vivo, particularly T-cell responses directed against self-antigens4. During infection by L. major, CD4+CD25+ T cells accumulate in the dermis, where they suppress—by both interleukin-10-dependent and interleukin-10-independent mechanisms—the ability of CD4+CD25- effector T cells to eliminate the parasite from the site. The sterilizing immunity achieved in mice with impaired IL-10 activity is followed by the loss of immunity to reinfection, indicating that the equilibrium established between effector and regulatory T cells in sites of chronic infection might reflect both parasite and host survival strategies.

Suggested Citation

  • Yasmine Belkaid & Ciriaco A. Piccirillo & Susana Mendez & Ethan M. Shevach & David L. Sacks, 2002. "CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity," Nature, Nature, vol. 420(6915), pages 502-507, December.
  • Handle: RePEc:nat:nature:v:420:y:2002:i:6915:d:10.1038_nature01152
    DOI: 10.1038/nature01152
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    Cited by:

    1. Dayakar Alti & Suresh Kumar Kalangi, 2018. "Trend of Regulatory T-Cells in the Pathogenesis of Leishmania Infection," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 10(5), pages 8083-8085, November.
    2. Anna-Lena Geiselhöringer & Daphne Kolland & Arisha Johanna Patt & Linda Hammann & Amelie Köhler & Luisa Kreft & Nina Wichmann & Miriam Hils & Christiane Ruedl & Marc Riemann & Tilo Biedermann & David , 2024. "Dominant immune tolerance in the intestinal tract imposed by RelB-dependent migratory dendritic cells regulates protective type 2 immunity," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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