Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4+ and CD8+ T lymphocyte responses
Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4+ and CD8+ T lymphocyte responses
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DOI：
10.1002/eji.200324840
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Letvin, NL
中科院分区：
文献类型：
--
作者：
McKay, PF;Barouch, DH;Letvin, NL
质粒DNA疫苗的免疫原性可能受到接种部位专职抗原呈递细胞（APC）可用性的限制。在这里，我们证明了募集到注射部位的APC类型可以选择性地调节由HIV-1 Env DNA疫苗在小鼠中引起的CD 4（+）或CD 8（+）T淋巴细胞应答。质粒GM-CSF与DNA疫苗的联合给药导致巨噬细胞向接种部位的募集，并特异性增强疫苗诱导的CD 4（+）T淋巴细胞应答。与此相反，质粒MIP-1 α与DNA疫苗联合给药导致树突状细胞募集到注射部位，并增强疫苗诱导的CD 8（+）T淋巴细胞应答。有趣的是，质粒GM-CSF和质粒MIP-1 α与DNA疫苗共同给药可募集巨噬细胞和树突状细胞，并导致CD 4（+）和CD 8（+）T淋巴细胞应答的协同和持续增强。这些数据表明，在确定由质粒DNA疫苗引起的免疫应答的程度和性质方面，当地招募的专业APC至关重要。此外，这些研究表明，不同的专业APC亚群可以选择性地调节DNA疫苗诱导的T淋巴细胞应答。
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-1alpha 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-1alpha 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.