Thu, 21 Aug 2008 15:05:45 BST CiteULike: AlfonsoVicenteSuarez's Kuchroo http://www.citeulike.org/user/AlfonsoVicenteSuarez/author/Kuchroo CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1402628 <i>J. Exp. Med., Vol. 204, No. 2. (19 February 2007), pp. 285-297.</i><br /><br />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-polarized 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-Foxp3- T cells in the chronic lesion. Nonetheless, only IL-10 production by antigen-specific CD4+CD25-Foxp3- T cells, the majority of which also produced IFN-gamma, was necessary for suppression of acquired immunity in Rag-/- reconstituted mice. Surprisingly, Rag-/- 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-producing Th1 cells, activated early in a strong inflammatory setting as a mechanism of feedback control, are the principal mediators of T cell-derived IL-10-dependent immune suppression in a chronic intracellular infection. 10.1084/jem.20061886 CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis Charles Anderson Mohammed Oukka Vijay Kuchroo David Sacks doi:10.1084/jem.20061886 J. Exp. Med., Vol. 204, No. 2. (19 February 2007), pp. 285-297. 2007-06-21T15:09:44-00:00 2007 J. Exp. Med. 204 2 285 297 il-10-tcells