Primed CD8(+) T-cell responses to allogeneic endothelial cells are controlled by local complement activation.
Publication/Presentation Date
8-1-2009
Abstract
CD8 T cells primed by transplantation recognize allogeneic class I MHC molecules expressed on graft vascular endothelium and contribute to allograft injury. We previously showed that immune cell-derived complement activation fragments are integral to T cell activation/expansion. Herein we tested the impact of local complement production/activation on T cell/endothelial cell (EC) interactions. We found that proinflammatory cytokines upregulated alternative pathway complement production by ECs, yielding C5a. We further found that ECs deficient in the cell surface C3/C5 convertase regulator decay accelerating factor (DAF, CD55) induced greater CD8 T-cell proliferation and more IFNgamma(+) and perforin(+) effector cells than wild-type (WT) ECs. Allogeneic C3(-/-) EC induced little or no CD8 responses. Abrogation of responses following C5a receptor (C5aR) blockade, or augmentation following addition of recombinant C5a demonstrated that the effects were mediated through T-cell-expressed-C5aR interactions. Analyses of in vivo CD8 cell responses to transplanted heart grafts deficient in EC DAF showed similar augmentation. The findings reveal that EC-derived complement triggers secondary CD8 T-cell differentiation and expansion and argue that targeting complement and/or C5aR could limit T-cell-mediated graft injury.
Volume
9
Issue
8
First Page
1784
Last Page
1795
ISSN
1600-6143
Published In/Presented At
Raedler, H., Yang, M., Lalli, P. N., Medof, M. E., & Heeger, P. S. (2009). Primed CD8(+) T-cell responses to allogeneic endothelial cells are controlled by local complement activation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 9(8), 1784–1795. https://doi.org/10.1111/j.1600-6143.2009.02723.x
Disciplines
Medicine and Health Sciences
PubMedID
19563342
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article