McKay Paul F, Barouch Dan H, Santra Sampa, Sumida Shawn M, Jackson Shawn S, Gorgone Darci A, Lifton Michelle A, Letvin Norman L
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02215, USA.
Eur J Immunol. 2004 Apr;34(4):1011-20. doi: 10.1002/eji.200324840.
The immunogenicity of plasmid DNA vaccines may be limited by the availability of professional antigen-presenting cells (APC) at the site of inoculation. Here we demonstrate that the types of APC recruited to the injection site can selectively modulate CD4(+) or CD8(+) T lymphocyte responses elicited by an HIV-1 Env DNA vaccine in mice. Coadministration of plasmid GM-CSF with the DNA vaccine resulted in the recruitment of macrophages to the site of inoculation and specifically augmented vaccine-elicited CD4(+) T lymphocyte responses. In contrast, coadministration of plasmid MIP-1 alpha with the DNA vaccine resulted in the recruitment of dendritic cells to the injection site and enhanced vaccine-elicited CD8(+) T lymphocyte responses. Interestingly, coadministration of both plasmid GM-CSF and plasmid MIP-1 alpha with the DNA vaccine recruited both macrophages and dendritic cells and led to a synergistic and sustained augmentation of CD4(+)and CD8(+) T lymphocyte responses. These data demonstrate the critical importance of locally recruited professional APC in determining the magnitude and nature of immune responses elicited by plasmid DNA vaccines. Moreover, these studies show that different subsets of professional APC can selectively modulate DNA vaccine-elicited T lymphocyte responses.
质粒DNA疫苗的免疫原性可能受到接种部位专业抗原呈递细胞（APC）可用性的限制。在此，我们证明募集到注射部位的APC类型可以选择性地调节HIV-1 Env DNA疫苗在小鼠体内引发的CD4(+)或CD8(+) T淋巴细胞反应。将质粒GM-CSF与DNA疫苗共同给药导致巨噬细胞募集到接种部位，并特异性增强了疫苗引发的CD4(+) T淋巴细胞反应。相反，将质粒MIP-1α与DNA疫苗共同给药导致树突状细胞募集到注射部位，并增强了疫苗引发的CD8(+) T淋巴细胞反应。有趣的是，将质粒GM-CSF和质粒MIP-1α与DNA疫苗共同给药会募集巨噬细胞和树突状细胞，并导致CD4(+)和CD8(+) T淋巴细胞反应协同且持续增强。这些数据证明了局部募集的专业APC在决定质粒DNA疫苗引发的免疫反应的强度和性质方面的至关重要性。此外，这些研究表明，专业APC的不同亚群可以选择性地调节DNA疫苗引发的T淋巴细胞反应。
