Koido Shigeo, Tanaka Yasuhiro, Chen Dongshu, Kufe Donald, Gong Jianlin
Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
J Immunol. 2002 Mar 1;168(5):2111-7. doi: 10.4049/jimmunol.168.5.2111.
Previous work has demonstrated that dendritic/tumor fusion cells induce potent antitumor immune responses in vivo and in vitro. However, little is known about the migration and homing of fusion cells after s.c. injection or the kinetics of CD4+ and CD8+ T cell activation. In the present study, fluorescence-labeled dendritic/MUC1-positive tumor fusion cells (FC/MUC1) were injected s.c. into MUC1-transgenic mice. The FC/MUC1 migrated to draining lymph nodes and were closely associated with T cells in a pattern comparable with that of unfused dendritic cells. Immunization of MUC1-transgenic mice with FC/MUC1 resulted in proliferation of T cells and induced MUC1-specific CD8+ CTL. Moreover, CD4+ T cells activated by FC/MUC1 were multifunctional effectors that produced IL-2, IFN-gamma, IL-4, and IL-10. These findings indicate that both CD4+ and CD8+ T cells can be primed in vivo by FC/MUC1 immunization.
先前的研究表明,树突状细胞/肿瘤融合细胞在体内和体外均可诱导强大的抗肿瘤免疫反应。然而,关于皮下注射后融合细胞的迁移和归巢,以及CD4+和CD8+ T细胞激活的动力学,人们了解甚少。在本研究中,将荧光标记的树突状细胞/MUC1阳性肿瘤融合细胞(FC/MUC1)皮下注射到MUC1转基因小鼠体内。FC/MUC1迁移至引流淋巴结,并与T细胞紧密关联,其模式与未融合的树突状细胞相似。用FC/MUC1免疫MUC1转基因小鼠可导致T细胞增殖,并诱导产生MUC1特异性CD8+ CTL。此外,由FC/MUC1激活的CD4+ T细胞是产生IL-2、IFN-γ、IL-4和IL-10的多功能效应细胞。这些发现表明,通过FC/MUC1免疫可在体内启动CD4+和CD8+ T细胞。