Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis.
Publication/Presentation Date
9-1-2008
Abstract
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 antigen-presenting cells (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, whereas T-cell expansion induced by C3(-/-) APCs was reduced because of 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 up-regulation. 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.
Volume
112
Issue
5
First Page
1759
Last Page
1766
ISSN
1528-0020
Published In/Presented At
Lalli, P. N., Strainic, M. G., Yang, M., Lin, F., Medof, M. E., & Heeger, P. S. (2008). Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis. Blood, 112(5), 1759–1766. https://doi.org/10.1182/blood-2008-04-151068
Disciplines
Medicine and Health Sciences
PubMedID
18567839
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article