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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3294-3301. Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-03-1214. This Article Full Text (PDF) All Versions of this Article: 2004-03-1214v1 104/10/3294    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Xystrakis, E. Articles by Saoudi, A. Search for Related Content PubMed PubMed Citation Articles by Xystrakis, E. Articles by Saoudi, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 1, 2004 Accepted June 29, 2004 Identification of a novel natural regulatory CD8 T-cell subset and analysis of its mechanism of regulation Emmanuel Xystrakis, Anne S Dejean, Isabelle Bernard, Philippe Druet, Roland Liblau, Daniel Gonzalez-Dunia, and Abdelhadi Saoudi* CPTP, INSERM Unite 563 and IFR30, Toulouse, France * Corresponding author; email: Abdelhadi.Saoudi{at}toulouse.inserm.fr. The immune system contains natural regulatory T cells that control the magnitude of the immune response during physiological and pathological conditions. Although this suppressive function was historically attributed to CD8 T cells, most recent reports have focused on natural regulatory CD4 T cells. In the present study, we describe a new subset of natural CD8 regulatory T cells in normal healthy animals. This subset expresses low levels of CD45RC at its surface (CD45RClow), produces mainly IL-4, IL-10 and IL-13 cytokines upon in vitro stimulation, expresses Foxp3 and CTLA-4, and is not cytotoxic against allogeneic targets. This subset suppresses the proliferation and differentiation of autologous CD4 T cells into type-1 cytokines producing T cells after stimulation with allogeneic accessory cells. We also provide evidence that this regulatory subset mediates its suppression by cell-to-cell contact and not through secretion of suppressive cytokines. Finally, the regulatory activity of CD8 CD45RClow cells is also demonstrated in vivo in a rat model of CD4-dependent Graft-versus Host Disease. Collectively, these data demonstrate for the first time that freshly isolated rat CD8 CD45RClow T cells contain T cells with regulatory properties, a result that enlarges the general figure of T cell mediated regulation. 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