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CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


J Am Soc Nephrol 15: 2414-2422, 2004
© 2004 American Society of Nephrology
doi: 10.1097/01.ASN.0000135974.06478.7B
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J Am Soc Nephrol 15:2414-2422, 2004
© 2004 American Society of Nephrology

BASIC SCIENCE

Complement Activation Regulates the Capacity of Proximal Tubular Epithelial Cell to Stimulate Alloreactive T Cell Response

Ke Li, Hetal Patel, Conrad A. Farrar, Roseanna E.G. Hargreaves, Steven H. Sacks and Wuding Zhou

Department of Nephrology and Transplantation, Guy’s Hospital, King’s College London, London, United Kingdom

Correspondence to Dr. Wuding Zhou, Department of Nephrology and Transplantation, 5th Floor, Thomas Guy House, Guy’s Hospital, London SE1 9RT, UK. Phone: 44-207-188-1528; Fax: 44-207-188-5660; E-mail: wuding.zhou{at}kcl.ac.uk

ABSTRACT. Tissue expression of C3 is an unexpected regulator of the alloimmune response in mouse kidney transplantation. It is unclear, however, whether a direct or an indirect action of complement on the host immune response is involved. Also unknown is which of the complement effector products, cleaved C3, cleaved C5, or C5b-9, is responsible. Proximal tubular epithelial cells (PTEC) not only constitute a major target of the alloimmune response but also produce substantial amounts of C3. This study investigated the property of mouse PTEC to stimulate alloreactive T cells in a complement-dependent manner. The proliferative and cytokine responses of primed alloreactive T cells were measured after exposure to donor-specific PTEC that had been pretreated with normal mouse serum, heat-inactivated mouse serum, or complement- deficient (C3, C5, or C6) mouse sera to differentially deposit complement components. PTEC were able to stimulate alloreactive T cells in an antigen-specific manner. Complement activation leading to the deposition of cleaved C3 on PTEC enhanced the alloreactive T cell response. This complement-mediated stimulation of the T cell response was dependent on C3 but not on C5 or C6. The primary influence of tissue-bound complement was on CD4+ T cells. Moreover, the effect of complement on alloreactive T cells was B7 dependent, shown by inhibition studies with CTLA4-Ig. These results suggest that donor epithelium-bound C3 can upregulate the alloimmune response. It is postulated that surface-bound C3 interacts with complement receptors on alloreactive T cells or on antigen presenting cells to increase allo-immune stimulation.




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[Abstract] [Full Text] [PDF]


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