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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2461-2469. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-08-3144. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2005-08-3144v1 107/6/2461    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 Zhou, W. Articles by Sacks, S. H. Search for Related Content PubMed PubMed Citation Articles by Zhou, W. Articles by Sacks, S. H. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells Wuding Zhou, Hetal Patel, Ke Li, Qi Peng, Marie-Bernadette Villiers, and Steven H. Sacks From the Department of Nephrology and Transplantation, King's College London School of Medicine at Guy's, King's College and St. Thomas' Hospitals, London, United Kingdom; and the Laboratoire d'Immunochimie, Commissariat à l'Energie Atomique de Grenoble (CEA-G), Département Réponse et Dynamique Cellulaire/Immunochimie (DRDC/ICH), Institut National de la Santé et de la Recherche Médicale (INSERM) U548, Université J. Fourier, Grenoble, France. Impaired T-cell reactivity is a feature of C3-deficient mice in several disease models. The mechanism behind the reduced T-cell response is, however, poorly understood. We explored the hypothesis that antigen-presenting cells (APCs) from C3-/- mice have impaired potency to stimulate antigen-specific T cells, in an alloantigen-dependent model. Our results show that C3-/- macrophages have reduced ability to elicit alloreactive T-cell responses in vitro and in vivo, affecting both the primary and secondary responses. The C3 status of donor macrophages had a major impact on the CD4 T-cell response. The impaired CD4 T-cell response was associated with reduced expression of MHC class II on the surface of C3-/- macrophages, without loss of class II gene expression. Furthermore, inhibition of C3 gene expression in C3+/+ macrophages reduced their ability to stimulate alloreactive T cells, suggesting that endogenous production of C3 could in part contribute to the potency of APCs. Our data provide compelling evidence that C3 deficiency modulates the potency of APCs to stimulate the T-cell response, suggesting a critical role for complement in the maintenance of APC function. This could offer a partial explanation as to why the T-cell response is impaired in C3-/- mice. (Blood. 2006;107:2461-2469) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Li, K. J. Anderson, Q. Peng, A. Noble, B. Lu, A. P. Kelly, N. Wang, S. H. Sacks, and W. Zhou Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation Blood, December 15, 2008; 112(13): 5084 - 5094. [Abstract] [Full Text] [PDF] Q. Peng, K. Li, K. Anderson, C. A. Farrar, B. Lu, R. A. G. Smith, S. H. Sacks, and W. Zhou Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction Blood, February 15, 2008; 111(4): 2452 - 2461. [Abstract] [Full Text] [PDF] Z. V. Popovic, R. Sandhoff, T. P. Sijmonsma, S. Kaden, R. Jennemann, E. Kiss, E. Tone, F. Autschbach, N. Platt, E. Malle, et al. Sulfated Glycosphingolipid as Mediator of Phagocytosis: SM4s Enhances Apoptotic Cell Clearance and Modulates Macrophage Activity J. Immunol., November 15, 2007; 179(10): 6770 - 6782. [Abstract] [Full Text] [PDF] P. N. Lalli, M. G. Strainic, F. Lin, M. E. Medof, and P. S. Heeger Decay Accelerating Factor Can Control T Cell Differentiation into IFN-{gamma}-Producing Effector Cells via Regulating Local C5a-Induced IL-12 Production J. Immunol., November 1, 2007; 179(9): 5793 - 5802. [Abstract] [Full Text] [PDF] K. M. Brown, E. Kondeatis, R. W. Vaughan, S. P. Kon, C. K.T. Farmer, J. D. Taylor, X. He, A. Johnston, C. Horsfield, B. J.C. Janssen, et al. Influence of donor C3 allotype on late renal-transplantation outcome. N. Engl. J. Med., May 11, 2006; 354(19): 2014 - 2023. [Abstract] [Full Text] [PDF]

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