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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2257-2264. Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-10-4059. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4059v1 108/7/2257    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Laffont, S. Articles by Guéry, J.-C. Search for Related Content PubMed PubMed Citation Articles by Laffont, S. Articles by Guéry, J.-C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CD8+ T-cell–mediated killing of donor dendritic cells prevents alloreactive T helper type-2 responses in vivo Sophie Laffont, Jérôme D. Coudert, Lucile Garidou, Laurent Delpy, Aurélie Wiedemann, Cécile Demur, Christiane Coureau, and Jean-Charles Guéry From Institut National de la Santé et de la Recherche Médicale (INSERM), U 563, Centre de Physiopathologie de Toulouse-Purpan, the Université Paul-Sabatier, and Service d'Hématologie, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse, France. Accumulating evidence indicates that, in absence of CD8+ T-cell activation, CD4+ T-cell–mediated allograft rejection is associated with a dominant Th2-cell response and eosinophil infiltrates. In this study, we analyzed the mechanisms by which CD8+ T cells regulate alloreactive CD4+ T-cell priming and differentiation into interleukin 4 (IL-4)–producing cells. We showed that interferon (IFN-) production by CD8+ T cells was dispensable for the inhibition of Th2-cell development, as well as tissue eosinophilia and type 2 cytokine production in the rejected grafts. Since we noticed that CD8+ T cells not only suppressed Th2 differentiation, but also down-modulated the overall priming of alloreactive CD4+ T cells, we evaluated whether CD8+ T cells act by limiting the accumulation of donor-derived dendritic cells (DCs) in lymph nodes. We found that indeed, alloreactive CD8+ T cells rapidly eliminated allogeneic DCs from T-cell areas of draining lymph nodes, through a perforin-dependent mechanism. Thus, our data demonstrate that cytotoxic T lymphocyte (CTL)–mediated clearance of allogeneic DCs is a negative feedback mechanism that limits the duration of alloantigen presentation in draining lymph nodes, thereby modulating the amplitude and polarization of the primary alloreactive CD4+ T-cell responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Douin-Echinard, S. Laffont, C. Seillet, L. Delpy, A. Krust, P. Chambon, P. Gourdy, J.-F. Arnal, and J.-C. Guery Estrogen Receptor {alpha}, but Not {beta}, Is Required for Optimal Dendritic Cell Differentiation and CD40-Induced Cytokine Production J. Immunol., March 15, 2008; 180(6): 3661 - 3669. [Abstract] [Full Text] [PDF] B. Gomes, M. D. Cabral, A. Gallard, M. Savignac, P. Paulet, P. Druet, B. Mariame, M. Moreau, C. Leclerc, J.-C. Guery, et al. Calcium Channel Blocker Prevents T Helper Type 2 Cell-mediated Airway Inflammation Am. J. Respir. Crit. Care Med., June 1, 2007; 175(11): 1117 - 1124. [Abstract] [Full Text] [PDF]

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