期刊
BLOOD
卷 112, 期 5, 页码 1759-1766出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-04-151068
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类别
资金
- National Institutes of Health, Bethesda, M D [AI43578, AI071185]
- Roche Organ Transplant Research Foundation, Meggen, Switzerland
- Ohio Affiliate of the American Heart Association (Columbus, Ohio)
- [AI23598]
- [EY11288]
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.
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