Tebbey P W, Hagen M, Hancock G E
Department of Immunology Research, Wyeth-Lederle Vaccines and Pediatrics, West Henrietta, New York 14586-9728, USA.
J Exp Med. 1998 Nov 16;188(10):1967-72. doi: 10.1084/jem.188.10.1967.
We analyzed the immune responses evoked by a series of overlapping peptides to better understand the molecular basis for respiratory syncytial virus (RSV) G protein-induced eosinophilia in BALB/c mice. In vitro stimulation of spleen cells from natural G protein-primed mice showed dominant proliferative and cytokine (interferon [IFN]-gamma and interleukin [IL]-5) responses to a peptide encompassing amino acids 184-198. Mice vaccinated with peptide 184- 198 conjugated to keyhole limpet hemocyanin showed significant pulmonary eosinophilia (39.5%) after challenge with live RSV. In contrast, mice immunized with a peptide (208-222) conjugate associated with induction of IFN-gamma secreting spleen cells did not exhibit pulmonary eosinophilia after challenge. The in vivo depletion of CD4(+) cells abrogated pulmonary eosinophilia in mice vaccinated with the peptide 184-198 conjugate, whereas the depletion of CD8(+) cells had a negligible effect. Therefore, we have identified an association between peptide 184- 198 of natural G protein and the CD4(+) T cell-mediated induction of pulmonary eosinophilia after live RSV challenge. Out of 43 human donors, 6 provided peripheral blood mononuclear cells that showed reactivity to G protein from RSV A2, 3 of which responded to peptide 184- 198. The results have important implications for the development of a vaccine against RSV.
我们分析了一系列重叠肽引发的免疫反应，以更好地理解呼吸道合胞病毒（RSV）G蛋白诱导BALB/c小鼠嗜酸性粒细胞增多的分子基础。对天然G蛋白致敏小鼠的脾细胞进行体外刺激，结果显示，针对包含氨基酸184 - 198的肽段，出现了占主导地位的增殖反应和细胞因子（干扰素[IFN]-γ和白细胞介素[IL]-5）反应。用与钥孔戚血蓝蛋白偶联的肽段184 - 198免疫的小鼠，在受到活RSV攻击后出现了显著的肺部嗜酸性粒细胞增多（39.5%）。相比之下，用与诱导IFN-γ分泌脾细胞相关的肽段（208 - 222）偶联物免疫的小鼠，在受到攻击后未出现肺部嗜酸性粒细胞增多。体内清除CD4(+)细胞消除了用肽段184 - 198偶联物免疫的小鼠的肺部嗜酸性粒细胞增多现象，而清除CD8(+)细胞的影响可忽略不计。因此，我们确定了天然G蛋白的肽段184 - 198与活RSV攻击后CD4(+) T细胞介导的肺部嗜酸性粒细胞增多诱导之间的关联。在43名人类供体中，6人提供的外周血单核细胞对RSV A2的G蛋白有反应，其中3人对肽段184 - 198有反应。这些结果对开发针对RSV的疫苗具有重要意义。
