The Journal of Experimental Medicine
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Published 19 November 2001. doi:10.1084/jem.194.10.1497
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© Rockefeller University Press, 0022-1007/2001/11/1497/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 10, November 19, 2001 1497-1506

Original Article

The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti–IL-10 Receptor Antibody for Sterile Cure

Yasmine Belkaid1, Karl F. Hoffmann1, Susana Mendez1, Shaden Kamhawi1, Mark C. Udey2, Tom A. Wynn1 and David L. Sacks1

1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
2 Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Address correspondence to Dr. D.L. Sacks, National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases, Bldg. 4, Rm. 126, Center Dr. MSC 0425, Bethesda, MD 20892-0425. Phone: 301-496-0577; Fax: 301-480-3708; E-mail: dsacks{at}nih.gov

Some pathogens (e.g., Mycobacterium tuberculosis, Toxoplasma gondii, Leishmania spp) have been shown to persist in their host after clinical cure, establishing the risk of disease reactivation. We analyzed the conditions necessary for the long term maintenance of Leishmania major in genetically resistant C57BL/6 mice after spontaneous healing of their dermal lesions. Interleukin (IL)-10 was found to play an essential role in parasite persistence as sterile cure was achieved in IL-10–deficient and IL-4/IL-10 double-deficient mice. The requirement for IL-10 in establishing latency associated with natural infection was confirmed in IL-10–deficient mice challenged by bite of infected sand flies. The host-parasite equilibrium was maintained by CD4+ and CD8+ T cells which were each able to release IL-10 or interferon (IFN)-{gamma}, and were found to accumulate in chronic sites of infection, including the skin and draining lymph node. A high frequency of the dermal CD4+ T cells released both IL-10 and IFN-{gamma}. Wild-type mice treated transiently during the chronic phase with anti–IL-10 receptor antibodies achieved sterile cure, suggesting a novel therapeutic approach to eliminate latency, infection reservoirs, and the risk of reactivation disease.

Key Words: Leishmania major • IL-10 • skin • chronic infection • CD8+ T cells


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