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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1759-1766. Prepublished online as a Blood First Edition Paper on June 20, 2008; DOI 10.1182/blood-2008-04-151068. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-151068v1 112/5/1759    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 Lalli, P. N Articles by Heeger, P. S Search for Related Content PubMed PubMed Citation Articles by Lalli, P. N Articles by Heeger, P. S Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 11, 2008 Accepted June 12, 2008 Locally produced C5a binds to T cell-expressed C5aR to enhance effector T cell expansion by limiting antigen-induced apoptosis Peter N Lalli, Michael G Strainic, Min Yang, Feng Lin, M Edward Medof, and Peter S Heeger* Immunology, The Cleveland Clinic, Cleveland, OH, United States Institute of Pathology, Case Western Reserve University, Cleveland, OH, United States Division of Nephrology, Dept of Medicine, Mt. Sinai School of Medicine, New York, NY, United States * Corresponding author; email: peter.heeger{at}mssm.edu. Our recent studies have shown that immune cell-produced complement provides costimulatory and survival signals to naive CD4+ T cells. Whether these signals are similarly required during effector cell expansion and what molecular pathways link locally produced complement to T cell survival were not clarified. To address this, we stimulated monoclonal and polyclonal T cells in vitro and in vivo with APCs deficient in the complement regulatory protein, decay accelerating factor (DAF), and/or the complement component C3. We found that T cell expansion induced by DAF-deficient APCs was augmented with diminished T cell apoptosis while T cell expansion induced by C3-/- APCs was reduced due to enhanced T cell apoptosis. These effects were traced to locally produced C5a, which through binding to T cell-expressed C5aR, enhanced expression of Bcl-2 and prevented Fas upregulation. The results show that C5aR signal transduction in T cells is important to allow optimal T cell expansion, as well as to maintain naive cell viability, and does so by suppressing programmed cell death. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Complement dances with T cells M. Javeed Ansari and Mohamed H. Sayegh Blood 2008 112: 1551-1552. [Full Text] [PDF] This article has been cited by other articles: F. An, Q. Li, Z. Tu, H. Bu, C.-C. Chan, R. R. Caspi, and F. Lin Role of DAF in Protecting against T-Cell Autoreactivity that Leads to Experimental Autoimmune Uveitis Invest. Ophthalmol. Vis. Sci., August 1, 2009; 50(8): 3778 - 3782. [Abstract] [Full Text] [PDF] Q. Li, K. Nacion, H. Bu, and F. Lin The Complement Inhibitor FUT-175 Suppresses T Cell Autoreactivity in Experimental Autoimmune Encephalomyelitis Am. J. Pathol., August 1, 2009; 175(2): 661 - 667. [Abstract] [Full Text] [PDF] C. Fang, X. Zhang, T. Miwa, and W.-C. Song Complement promotes the development of inflammatory T-helper 17 cells through synergistic interaction with Toll-like receptor signaling and interleukin-6 production Blood, July 30, 2009; 114(5): 1005 - 1015. [Abstract] [Full Text] [PDF] N. S. Sheerin Should Complement Activation Be a Target for Therapy in Renal Transplantation? J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2250 - 2251. [Full Text] [PDF]

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