{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:20:15Z","timestamp":1791145215558,"version":"4.1.0"},"reference-count":62,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,2,19]]},"abstract":"<jats:p>Nonhealing forms of leishmaniasis in humans are commonly associated with elevated levels of the deactivating cytokine IL-10, and in the mouse, normally chronic infections can be cleared in the absence of IL-10. Using a Leishmania major strain that produces nonhealing dermal lesions in a T helper type 1 (Th1) cell\u2013polarized setting, we have analyzed the cellular sources of IL-10 and their relative contribution to immune suppression. IL-10 was produced by innate cells, as well as CD4+CD25+Foxp3+ and CD4+CD25\u2212Foxp3\u2212 T cells in the chronic lesion. Nonetheless, only IL-10 production by antigen-specific CD4+CD25\u2212Foxp3\u2212 T cells, the majority of which also produced IFN-\u03b3, was necessary for suppression of acquired immunity in Rag\u2212\/\u2212 reconstituted mice. Surprisingly, Rag\u2212\/\u2212 mice reconstituted with naive CD4+ T cells depleted of natural T regulatory cells developed more severe infections, associated with elevated levels of IL-10 and, especially, Th2 cytokines in the site. The data demonstrate that IL-10\u2013producing Th1 cells, activated early in a strong inflammatory setting as a mechanism of feedback control, are the principal mediators of T cell\u2013derived IL-10\u2013dependent immune suppression in a chronic intracellular infection.<\/jats:p>","DOI":"10.1084\/jem.20061886","type":"journal-article","created":{"date-parts":[[2007,2,5]],"date-time":"2007-02-05T20:36:49Z","timestamp":1170707809000},"page":"285-297","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":462,"title":["CD4+CD25\u2212Foxp3\u2212 Th1 cells are the source of IL-10\u2013mediated immune suppression in chronic cutaneous leishmaniasis"],"prefix":"10.1084","volume":"204","author":[{"given":"Charles F.","family":"Anderson","sequence":"first","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Oukka","sequence":"additional","affiliation":[{"name":"2Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay J.","family":"Kuchroo","sequence":"additional","affiliation":[{"name":"2Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sacks","sequence":"additional","affiliation":[{"name":"1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,2,5]]},"reference":[{"key":"2023072515580796400_BIB1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nri933","volume":"2","year":"2002","journal-title":"Nat. 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