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Local synthesis of complement component C3 regulates acute renal transplant rejection

Nature Medicine volume 8, pages 582–587 (2002)Cite this article

Abstract

Accumulating evidence suggests that innate immunity interacts with the adaptive immune system to identify potentially harmful antigens and eliminate them from the host. A central facet of innate immunity is complement, which for some time has been recognized as a contributor to inflammation in transplant rejection but without detailed analysis of its role in what is principally a T cell–mediated process. Moreover, epithelial and vascular tissues at local sites of inflammation secrete complement components; however, the role of such local synthesis remains unclear. Here we show that the absence of locally synthesized complement component C3 is capable of modulating the rejection of renal allografts in vivo and regulating T-cell responses in vivo and in vitro. The results indicate that improved success in kidney transplantation could come from therapeutic manipulation of innate immunity in concert with T cell–directed immunosuppression.

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Figure 1: Effect of deficient local C3 synthesis on transplant survival and function.
Figure 2: Localization of C3 mRNA and protein in transplanted tissues.
Figure 3: Mixed lymphocyte reaction in recipients of wild-type or C3−/− grafts.
Figure 4: Allostimulation with PTEC.
Figure 5: Expansion of CD4+CR1/2+ murine splenocytes after in vitro stimulation.
Figure 6: Phenotype of CD4+CR1/2+ cells in rejecting transplant recipients.

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  1. Department of Nephrology & Transplantation, King's College University of London, Guy's Hospital, London, UK

    Julian R. Pratt, Shamim A. Basheer & Steven H. Sacks

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  2. Shamim A. Basheer
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Correspondence to Steven H. Sacks.

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Pratt, J., Basheer, S. & Sacks, S. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med 8, 582–587 (2002). https://doi.org/10.1038/nm0602-582

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