1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
2. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
3. Present address: Research Foundation, Division of Molecular Immunology, Children's Hospital, 3333 Burnet Avenue, Cincinnati, Ohio, MLC 7021 452229, USA.
4. These authors contributed equally to this work

Correspondence to: Yasmine Belkaid^1,2,3 Correspondence and requests for materials should be addressed to Y.B. (e-mail: Email: yasmine.belkaid@cchmc.org).

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 reactivation^{1, 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.