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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 4, 2005 Accepted November 8, 2005 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 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 Laboratoire d'Immunochimie, CEA-G, DRDC/ICH, INSERM U548, Universite J. Fourier, Grenoble, France * Corresponding author; email: wuding.zhou{at}kcl.ac.uk. 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. 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