Sun, 27 Jul 2008 06:02:01 BST CiteULike: AlfonsoVicenteSuarez's il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/tag/il-10-tcells CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2893635 <i>J. Exp. Med., Vol. 205, No. 6. (9 June 2008), pp. 1381-1393.</i><br /><br />The nuclear hormone receptor retinoic acid receptor-related orphan receptor gammat (RORgammat) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of RORgammat+ T cells express IL-17. We report here that RORgammat+ Talpha cells include Foxp3+ cells that coexist with IL-17-producing RORgammat+ Talpha cells in all tissues examined. The Foxp3+ RORgammat+ Talpha express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3+ to IL-17-producing RORgammat+ Talpha cells remains remarkably constant in mice enduring infection and inflammation. This equilibrium is tuned in favor of IL-10 production by Foxp3 and CCL20, and in favor of IL-17 production by IL-6 and IL-23. In the lung and skin, the largest population of RORgammat+ T cells express the gammadelta T cell receptor and produce the highest levels of IL-17 independently of IL-6. Thus, potentially antagonistic proinflammatory IL-17-producing and regulatory Foxp3+ RORgammat+ T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in RORgammat+ T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation. 10.1084/jem.20080034 In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgammat+ T cells Matthias Lochner Lucie Peduto Marie Cherrier Shinichiro Sawa Francina Langa Rosa Varona Dieter Riethmacher Mustapha Si-Tahar James Di Santo Gerard Eberl doi:10.1084/jem.20080034 J. Exp. Med., Vol. 205, No. 6. (9 June 2008), pp. 1381-1393. 2008-06-13T23:05:58-00:00 2008 J. Exp. Med. 205 6 1381 1393 il-10-tcells th17 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1447009 <i>J. Exp. Med., Vol. 190, No. 7. (4 October 1999), pp. 995-1004.</i><br /><br />A T helper cell type 1-mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population can be reversed in vivo by administration of an anti-transforming growth factor beta antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population. This population isolated from IL-10-deficient (IL-10-/-) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti-murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RBlow CD4+ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RBhigh CD4+ cells, as CD45RBlow CD4+ cells from WT mice were able to inhibit colitis induced by IL-10-/- CD45RBhigh CD4+ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens. 10.1084/jem.190.7.995 An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation Chrystelle Asseman Smita Mauze Michael Leach Robert Coffman Fiona Powrie doi:10.1084/jem.190.7.995 J. Exp. Med., Vol. 190, No. 7. (4 October 1999), pp. 995-1004. 2007-07-10T16:27:33-00:00 1999 J. Exp. Med. 190 7 995 1004 il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1417145 <i>Semin Immunol, Vol. 18, No. 2. (April 2006), pp. 120-127.</i><br /><br />Peripheral tolerance is mediated by multiple mechanisms such as anergy and/or active suppression of effector T cells by T regulatory (Tr) cells. Among the CD4(+) Tr cells, T regulatory type 1 cells (Tr1) have been shown to down-modulate immune responses through production of the immunosuppressive cytokines IL-10 and TGF-beta. Tr1 cells maintain peripheral tolerance, control autoimmunity, and prevent allograft rejection and graft versus host disease (GvHD). Cellular therapy with ex vivo generated Tr1 cells has been proven to be effective in several preclinical models of T cell-mediated pathologies and therefore, represents a promising approach for clinical application. This review will summarize the new findings on Tr1 cells, the recent development of methods for their ex vivo expansion, and their potential clinical relevance as cellular therapy. Tr1 cells: from discovery to their clinical application. M Battaglia S Gregori R Bacchetta MG Roncarolo doi:10.1016/j.smim.2006.01.007 Semin Immunol, Vol. 18, No. 2. (April 2006), pp. 120-127. 2007-06-27T18:58:00-00:00 2006 Semin Immunol 1044-5323 18 2 120 127 il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1414472 <i></i> CD4 T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4 T cells -- Morrissey et al. 178 (1): 237 -- The Journal of Experimental Medicine 2007-06-26T19:38:23-00:00 il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1414229 <i>Nature, Vol. 389, No. 6652. (16 October 1997), pp. 737-742.</i> A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis Herve Groux Anne O'Garra Mike Bigler Matthieu Rouleau Svetlana Antonenko Jan de Vries Maria Roncarolo doi:10.1038/39614 Nature, Vol. 389, No. 6652. (16 October 1997), pp. 737-742. 2007-06-26T16:46:25-00:00 1997 Nature 389 6652 737 742 il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/773726 <i>Immunological Reviews, Vol. 212, No. 1. (August 2006), pp. 28-50.</i> Interleukin10secreting type 1 regulatory T cells in rodents and humans Grazia Roncarolo Maria Gregori Silvia Battaglia Manuela Bacchetta Rosa Fleischhauer Katharina Levings K Megan doi:10.1111/j.0105-2896.2006.00420.x Immunological Reviews, Vol. 212, No. 1. (August 2006), pp. 28-50. 2006-07-25T21:33:32-00:00 2006 Immunological Reviews 0105-2896 212 1 28 50 Blackwell Publishing il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1333504 <i>Nature Reviews Immunology, Vol. 7, No. 6., pp. 425-428.</i> TH1 cells control themselves by producing interleukin-10 Anne O'Garra Paulo Vieira doi:10.1038/nri2097 Nature Reviews Immunology, Vol. 7, No. 6., pp. 425-428. 2007-05-25T19:44:10-00:00 Nature Reviews Immunology 1474-1733 7 6 425 428 Nature Publishing Group il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1402638 <i>J. Exp. Med., Vol. 194, No. 10. (19 November 2001), pp. 53F-57.</i><br /><br />10.1084/jem.194.10.f53 Regulatory Role of T Cells Producing both Interferon gamma and Interleukin 10 in Persistent Infection Giorgio Trinchieri doi:10.1084/jem.194.10.f53 J. Exp. Med., Vol. 194, No. 10. (19 November 2001), pp. 53F-57. 2007-06-21T15:16:18-00:00 2001 J. Exp. Med. 194 10 53F 57 il-10-tcells http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1402632 <i>J. Exp. Med., Vol. 204, No. 2. (19 February 2007), pp. 273-283.</i><br /><br />Although interferon gamma (IFN-gamma) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-gamma effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-gamma-secreting T-bet+Foxp3- T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10+IFN-gammagamma population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-gamma, IL-10 production could be stimulated in IL-10-IFN-gamma+ cells by further activation in vitro. In addition, experiments with T. gondii-specific IL-10+IFN-gamma+ CD4 clones revealed that although IFN-gamma expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4+ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens. 10.1084/jem.20062175 Conventional T-bet+Foxp3- Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection Dragana Jankovic Marika Kullberg Carl Feng Romina Goldszmid Carmen Collazo Mark Wilson Thomas Wynn Masahito Kamanaka Richard Flavell Alan Sher doi:10.1084/jem.20062175 J. Exp. Med., Vol. 204, No. 2. (19 February 2007), pp. 273-283. 2007-06-21T15:11:34-00:00 2007 J. Exp. Med. 204 2 273 283 il-10-tcells 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 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1402623 <i>J. Exp. Med., Vol. 204, No. 2. (19 February 2007), pp. 239-243.</i><br /><br />Interleukin (IL)-10 is a cytokine that modulates both innate and adaptive immunity, primarily by exerting antiinflammatory effects. IL-10 was originally thought to be produced only by T helper (Th)2 cells, but is now known to be made by a variety of cell types. During many infections, CD4+ T cells produce both interferon (IFN)-gamma, the signature Th1 cytokine, and IL-10. New data now show that the IL-10 produced by effector Th1 cells helps limit the collateral damage caused by exaggerated inflammation. But this control may also limit the effectiveness of the immune response, resulting in a failure to fully eliminate pathogens. 10.1084/jem.20070104 Interleukin-10 production by effector T cells: Th1 cells show self control Giorgio Trinchieri doi:10.1084/jem.20070104 J. Exp. Med., Vol. 204, No. 2. (19 February 2007), pp. 239-243. 2007-06-21T15:06:46-00:00 2007 J. Exp. Med. 204 2 239 243 il-10-tcells