B lymphocytes participate in cross-presentation of antigen following gene gun vaccination
B lymphocytes participate in cross-presentation of antigen following gene gun vaccination
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DOI：
10.4049/jimmunol.174.9.5233
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Jacob, J
中科院分区：
文献类型：
--
作者：
Hon, H;Oran, A;Jacob, J
虽然内吞蛋白通常通过II类MHC途径呈递刺激CD4(+) T细胞，但专业apc也可以交叉呈递Ags，因此这些外源肽可以与I类MHC络合以交叉启动CD8(+) T细胞。尽管树突状细胞（dc）交叉呈递Ags的能力已被充分证明，但尚不清楚其他apc是否也可能发挥作用，或者交叉引物对DNA免疫后获得性免疫的诱导作用的相对贡献是什么。在这项研究中，我们比较了由传统CMV启动子、dc特异性CD11c启动子或角化细胞特异性K14启动子驱动的DNA疫苗质粒在基因枪接种小鼠后产生的免疫应答。随着时间的推移，CD11c启动子在引流淋巴结的CD11c(+) dc中实现了相同的表达，与传统的cmv驱动质粒一样。然而，尽管从淋巴结分离的CD11c（+）细胞能够直接刺激ag特异性T细胞的体外增殖，但dc限制性DNA疫苗免疫未能对模型Ags流感血凝素和OVA产生保护性免疫或细胞免疫。相反，角化细胞限制性疫苗引发的T细胞和B细胞活性与传统的巨细胞病毒启动子驱动疫苗相当，这表明交叉启动在基因枪免疫后产生免疫反应中起主要作用。此外，在B细胞缺陷的mu-MT小鼠中进行的平行研究表明，除了dc外，B淋巴细胞还介导了ag特异性T细胞的交叉启动。总的来说，这些数据表明免疫原的广泛表达是最佳诱导保护性获得性免疫所必需的。
Although endocytosed proteins are commonly presented via the class II MHC pathway to stimulate CD4(+) T cells, professional APCs can also cross-present Ags, whereby these exogenous peptides can be complexed with class I MHC for cross-priming of CD8(+) T cells. Whereas the ability of dendritic cells (DCs) to cross-present Ags is well documented, it is not known whether other APCs may also play a role, or what is the relative contribution of cross-priming to the induction of acquired immunity after DNA immunization. In this study, we compared immune responses generated after gene gun vaccination of mice with DNA vaccine plasmids driven by the conventional CMV promoter, the DC-specific CD11c promoter, or the keratinocyte-specific K14 promoter. The CD11c promoter achieved equivalent expression in CD11c(+) DCs in draining lymph nodes over time, as did a conventional CMV-driven plasmid. However, immunization with DC-restricted DNA vaccines failed to generate protective Immoral or cellular immunity to model Ags influenza hemagglutinin and OVA, despite the ability of CD11c(+) cells isolated from lymph nodes to stimulate proliferation of Ag-specific T cells directly ex vivo. In contrast, keratinocyte-restricted vaccines elicited comparable T and B cell activity as conventional CMV promoter-driven vaccines, indicating that cross-priming plays a major role in the generation of immune responses after gene gun immunization. Furthermore, parallel studies in B cell-deficient mu-MT mice demonstrated that B lymphocytes, in addition to DCs, mediate cross-priming of Ag-specific T cells. Collectively, these data indicate that broad expression of the immunogen is required for optimal induction of protective acquired immunity.