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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 (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 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 Guery, J.-C. Search for Related Content PubMed PubMed Citation Articles by Laffont, S. Articles by Guery, J.-C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 12, 2005 Accepted January 21, 2006 CD8+ T cell-mediated killing of donor dendritic cells prevents alloreactive T helper type-2 responses in vivo Sophie Laffont, Jerome D Coudert, Lucile Garidou, Laurent Delpy, Aurelie Wiedemann, Cecile Demur, Christiane Coureau, and Jean-Charles Guery* INSERM, U563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France INSERM, U563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France; Service d'Hematologie, Centre Hospitalier Universitaire Purpan, Toulouse, France * Corresponding author; email: jean-charles.guery{at}toulouse.inserm.fr. 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 IL-4-producing cells. We showed that 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 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 the 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: Y. Matsunaga, D. Fukuma, S. Hirata, S. Fukushima, M. Haruta, T. Ikeda, I. Negishi, Y. Nishimura, and S. Senju Activation of Antigen-Specific Cytotoxic T Lymphocytes by {beta}2-Microglobulin or TAP1 Gene Disruption and the Introduction of Recipient-Matched MHC Class I Gene in Allogeneic Embryonic Stem Cell-Derived Dendritic Cells J. Immunol., November 1, 2008; 181(9): 6635 - 6643. [Abstract] [Full Text] [PDF] S. Laffont, C. Seillet, J. Ortaldo, J. D. Coudert, and J.-C. Guery Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells Blood, August 1, 2008; 112(3): 661 - 671. [Abstract] [Full Text] [PDF] 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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