von Bergwelt-Baildon Michael, Shimabukuro-Vornhagen Alexander, Popov Alexey, Klein-Gonzalez Nela, Fiore Francesca, Debey Svenja, Draube Andreas, Maecker Britta, Menezes Isaura, Nadler Lee M, Schultze Joachim L
Molecular Tumor Biology and Tumor Immunology, Clinic I of Internal Medicine, Hematology/Oncology, Kerpener Str 62, 50924 Köln, Germany.
Blood. 2006 Apr 1;107(7):2786-9. doi: 10.1182/blood-2004-01-0113. Epub 2005 Dec 15.
CD40-activated B cells (CD40-B cells) have previously been introduced as an alternative source of antigen-presenting cells for immunotherapy. CD40-B cells can prime naive and expand memory T cells, and they can be generated in large numbers from very small amounts of peripheral blood derived from healthy individuals or cancer patients alike. Administration of CD40-B cells as a cellular adjuvant would require these cells to migrate toward secondary lymphoid organs and attract T cells in situ, processes guided by specific chemokines and chemokine receptors. Here, we demonstrate that primary, human CD40-B cells express a pattern of adhesion molecules and chemokine receptors necessary for homing to secondary lymphoid organs and have the capacity to migrate to cognate ligands. Furthermore, we show that CD40-B cells express important T-cell attractants and induce strong T-cell chemotaxis. These findings further support the use of CD40-B cells as cellular adjuvant for cancer immunotherapy.
CD40激活的B细胞(CD40-B细胞)此前已被引入作为免疫治疗中抗原呈递细胞的替代来源。CD40-B细胞可以启动幼稚T细胞并扩增记忆T细胞,并且它们可以从极少量来自健康个体或癌症患者的外周血中大量产生。将CD40-B细胞作为细胞佐剂给药将要求这些细胞向二级淋巴器官迁移并在原位吸引T细胞,这些过程由特定的趋化因子和趋化因子受体引导。在这里,我们证明原代人CD40-B细胞表达归巢至二级淋巴器官所需的粘附分子和趋化因子受体模式,并具有迁移至同源配体的能力。此外,我们表明CD40-B细胞表达重要的T细胞吸引剂并诱导强烈的T细胞趋化性。这些发现进一步支持将CD40-B细胞用作癌症免疫治疗的细胞佐剂。