CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis

@article{citeulike:1402628, abstract = {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}, author = {Anderson, Charles F. and Oukka, Mohammed and Kuchroo, Vijay J. and Sacks, David }, citeulike-article-id = {1402628}, doi = {10.1084/jem.20061886}, journal = {J. Exp. Med.}, keywords = {il-10-tcells}, month = {February}, number = {2}, pages = {285--297}, posted-at = {2007-06-21 16:09:57}, priority = {2}, title = {CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis}, url = {http://dx.doi.org/10.1084/jem.20061886}, volume = {204}, year = {2007} }

TY - JOUR ID - citeulike:1402628 L3 - citeulike-article-id:1402628 TI - CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis JF - J. Exp. Med. VL - 204 IS - 2 SP - 285 EP - 297 N2 - 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 KW - il-10-tcells AU - Anderson, Charles AU - Oukka, Mohammed AU - Kuchroo, Vijay AU - Sacks, David PY - 2007/02/19/ UR - http://dx.doi.org/10.1084/jem.20061886 ER -