Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice

Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice
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DOI:
10.1128/iai.64.11.4456-4462.1996
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发表时间:
1996-11-01
影响因子:
3.1
通讯作者:
Bondada, S
Bondada, S
中科院分区:
医学2区
文献类型:
--
作者:
Garg, M;Luo, W;Bondada, S

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先前,在我们的实验室中开发了模型系统以研究鼠对23价肺炎球菌多糖疫苗Pnu-Immune的体内和体外免疫应答(M.加格和B。Subbarao,感染。Immun. 60:2329-2336,1992; M.加格A。M. Kaplan和S. 152:1589-1596,1994)。使用这些系统,我们发现老年小鼠在体内或体外对疫苗没有反应。细胞分离研究表明,老年脾细胞对疫苗的无反应性不是由于固有的B细胞缺陷或T细胞介导的免疫抑制,而是由于辅助细胞缺乏。来自年轻小鼠的辐射脾细胞使老年小鼠的脾细胞对疫苗产生反应。有趣的是,来自老年小鼠的辐射脾细胞也恢复了老年小鼠的疫苗应答,但需要比年轻小鼠脾细胞更多的数量才能诱导类似水平的应答。辅助细胞是一种贴壁细胞,可以通过Sephadex G-10去除,因此可能是巨噬细胞。辅助功能也可以由细胞因子白细胞介素-1(IL-1)、IL-4或IL-5提供,但不能由IL-2或IL-6提供。因此,老年小鼠对肺炎球菌疫苗免疫应答不足的一个原因是粘附辅助细胞的数量缺陷。
Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152:1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studied showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell deficiency. Irradiated spleen cells from young mice enabled the old mouse spleen cells to respond to the vaccine. Interestingly, irradiated spleen cells from old mice also restored the vaccine responsiveness in old mice but were required in greater numbers than the young mouse spleen cells to induce similar levels of response. The accessory cell was an adherent cell that could be removed by passage through Sephadex G-10 and thus may be a macrophage. Accessory function could also be provided by the cytokine interleukin-1 (IL-1), IL-4, or IL-5 but not IL-2 or IL-6. Thus, one reason for the deficient immune response to pneumococcal vaccine in aged mice is quantitative defect in adherent accessory cells.