TACI-BLyS signaling via B-cell-dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo
TACI-BLyS signaling via B-cell-dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo
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DOI：
10.1182/blood-2004-12-4708
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发表时间：
2006-01-15
期刊：
影响因子：
20.3
通讯作者：
Franco, A
中科院分区：
文献类型：
--
作者：
Diaz-de-Durana, Y;Mantchev, GT;Franco, A
我们证明了B细胞-树突状细胞（DC）通过跨膜激活剂和钙调节剂和亲环素配体（CAML）相互作用物（TACI）和B淋巴细胞刺激物（BLyS）的相互作用提供了早期信号，该信号对于产生足够数量的成熟抗原呈递细胞（APC）以在体内引发初始CD 8（+）T细胞（CTL）至关重要。有证据表明，B细胞是小鼠有效产生CTL所必需的，并且用野生型而不是TACI敲除的B细胞重建恢复了正常的CTL应答，这支持了我们的结论。此外，低剂量的表达TACI胞外结构域（氨基酸[aa] 1-126）的TACI融合蛋白（TACI-Fc）在体内恢复B细胞缺陷小鼠中的CTL引发，并在体外诱导DC成熟。事实上，在与B细胞相互作用后，脾DC快速表达CD 86共刺激分子，其表达程度与暴露于抗原刺激物相当。BLyS（高）肽脉冲的骨髓来源的DC，用作体内疫苗，不能在B细胞缺陷型和TACI缺陷型小鼠中产生CTL，强烈支持在CTL体内首次遇到抗原期间通过TACI-BLyS进行B细胞-DC合作的需要。
We demonstrated that B-cell-dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8(+) T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell-deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyS(high) peptide-pulsed bone marrow-derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell-deficient and TACI-deficient mice, strongly supporting a need for B-cell-DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.