The induction of HIV gag-specific CD8+ T cells in the spleen and gut-associated lymphoid tissue by parenteral or mucosal immunization with recombinant Listeria monocytogenes HIV gag
The induction of HIV gag-specific CD8+ T cells in the spleen and gut-associated lymphoid tissue by parenteral or mucosal immunization with recombinant Listeria monocytogenes HIV gag
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DOI：
10.4049/jimmunol.170.10.5176
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发表时间：
2003-05-15
影响因子：
4.4
通讯作者：
Paterson, Y
中科院分区：
文献类型：
--
作者：
Peters, C;Peng, XH;Paterson, Y
粘膜免疫的诱导对于控制 HIV 感染期间的病毒复制至关重要。在本研究中，我们比较了表达和分泌 HIV Ag Gag 的重组单核细胞增多性李斯特菌在脾脏、肠系膜淋巴结和派尔氏淋巴结中诱导针对该 Ag 的 CD8(+) T 细胞的能力，以及在静脉注射、口服或直肠施用疫苗后向固有层提供效应器 Gag 特异性 CD8(+) T 细胞的能力。使用IFN-γ细胞内细胞因子染色和H-2K(d) Gag肽四聚体染色离体测量Ag特异性CD8(+)激活T细胞的水平。我们发现所有免疫途径都会在脾脏中诱导Gag特异性CD8(+) T细胞。继发感染后，我们观察到脾脏中 CD8+ T 细胞的水平显着增加，并且 Gag 特异性细胞的水平与单核细胞增生李斯特菌的免疫显性 Ag 的李斯特菌溶血素 O 的水平相似。初次和二次口服免疫均导致固有层中产生丰富的Gag特异性CD8(+)激活T细胞，其构成类似于CD8区室的35%。然而，仅在两次免疫后才在粘膜淋巴组织中观察到显着水平的Gag和李斯特氏菌溶血素O特异性CD8+T细胞，这可能是因为它们在单次免疫后已经进入固有层隔室。在艾滋病毒的背景下，粘膜注射疫苗似乎最能促进能够预防感染的免疫反应。本报告中提供的数据表明，粘膜施用李斯特菌可以促进这种反应，并且加强剂量可以维持这种反应。
The induction of mucosal immunity is crucial in controlling viral replication during HIV infection. In this study we compare the ability of a recombinant Listeria monocytogenes that expresses and secretes the HIV Ag Gag to induce CD8(+) T cells against this Ag in the spleen, mesenteric lymph nodes, and Peyer's patches and the ability to provide effector Gag-specific CD8(+) T cells to the lamina propria after i.v., oral, or rectal administration of the vaccine. The levels of Ag-specific CD8(+)-activated T cells were measured ex vivo using intracellular cytokine staining for IFN-gamma and H-2K(d) Gag peptide tetramer staining. We found that all routes of immunization induced Gag-specific CD8(+) T cells in the spleen. After secondary infection, we observed substantial increases in splenic levels of CD8(+) T cells, and levels of Gag-specific cells were similar to those against listeriolysin O, the immunodominant Ag of L monocytogenes. Both primary and secondary oral immunization resulted in abundant Gag-specific CD8(+)-activated T cells in the lamina propria that constituted similar to35% of the CD8 compartment. However, significant levels of Gag and listeriolysin O-specific CD8(+) T cells were observed in mucosal lymphoid tissue only after two immunizations, perhaps because they had already entered the lamina propria compartment after a single immunization. In the context of HIV, a mucosally administered vaccine seems best calculated to prompt an immune response that is capable of preventing infection. The data presented in this report demonstrate that mucosally administered Listeria can prompt such a response and that booster doses can maintain this response.