Song E S, Lee V, Surh C D, Lynn A, Brumm D, Jolly D J, Warner J F, Chada S
Department of Immunobiology, Chiron Technology-Center for Gene Therapy, San Diego, CA 92121, USA.
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1943-8. doi: 10.1073/pnas.94.5.1943.
We have examined mechanisms involved in gene transfer, protein expression, and antigen presentation after direct administration of retroviral vectors using a variety of antigen systems. We have identified transduced infiltrating cells at the injection site, and the majority of the infiltrating cells were of the monocyte/macrophage lineage. We found that the splenic dendritic cell fraction contained proviral DNA, expressed antigenic proteins, and was able to present antigens efficiently to the immune system. Furthermore, the dendritic cell fractions from retroviral vector-immunized mice were able to prime naive T cells in vitro, and adoptive transfer of in vitro-transduced dendritic cell fractions elicited antigen-specific cytotoxic T lymphocytes. These data suggest a role for dendritic cells in induction of immune responses elicited by retroviral vector-mediated gene transfer.
我们使用多种抗原系统,研究了直接注射逆转录病毒载体后基因转移、蛋白质表达和抗原呈递所涉及的机制。我们在注射部位鉴定出了转导的浸润细胞,并且大多数浸润细胞属于单核细胞/巨噬细胞谱系。我们发现脾树突状细胞部分含有前病毒DNA,表达抗原蛋白,并且能够有效地将抗原呈递给免疫系统。此外,来自逆转录病毒载体免疫小鼠的树突状细胞部分能够在体外激活幼稚T细胞,体外转导的树突状细胞部分的过继转移引发了抗原特异性细胞毒性T淋巴细胞。这些数据表明树突状细胞在逆转录病毒载体介导的基因转移所引发的免疫反应诱导中发挥作用。