CD4+ T cell-independent vaccination against Pneumocystis carinii in mice
CD4+ T cell-independent vaccination against Pneumocystis carinii in mice
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DOI：
10.1172/jci13826
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发表时间：
2001-11-01
影响因子：
15.9
通讯作者：
Kolls, JK
中科院分区：
文献类型：
--
作者：
Zheng, MQ;Shellito, JE;Kolls, JK
在HIV感染的宿主中，由于CD4（+）T淋巴细胞的进行性耗竭，宿主防御受到严重损害。此外，CD4（+）T淋巴细胞缺陷会损害预防机会性感染的疫苗接种方法。因此，我们研究了一种不依赖于CD4（+）T细胞的疫苗方法来治疗典型的艾滋病定义感染，卡氏肺孢子虫（PC）肺炎。在这里，我们表明，骨髓来源的树突状细胞（DC）表达的小鼠CD40配体，当脉冲离体PC抗原，引起显着滴度和PC IgG在CD4缺陷小鼠。接种疫苗的动物表现出对PC感染的显著保护，并且这种保护是有效体液应答的结果，因为CD4耗尽的脾细胞或血清的过继转移赋予了这种对CD4缺陷小鼠的保护。PC抗原的Western印迹分析显示，DC接种，CD4缺陷型小鼠主要反应的55 kDa的PC抗原。这些研究显示了在针对HIV相关病原体的CD4非依赖性疫苗接种方面取得进展的希望。
Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4(+) T lymphocytes. Moreover, deficient CD4(+) T lymphocytes impair vaccination approaches to prevent opportunistic infection. Therefore, we investigated a CD4(+) T cell-independent vaccine approach to a prototypic AIDS-defining infection, Pneumocystis carinii (PC) pneumonia. Here, we demonstrate that bone marrow-derived dendritic cells (DCs) expressing the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited significant titers of and-PC IgG in CD4-deficient mice. Vaccinated animals demonstrated significant protection from PC infection, and this protection was the result of an effective humoral response, since adoptive transfer of CD4-depleted splenocytes or serum conferred this protection to CD4-deficient mice. Western blot analysis of PC antigen revealed that DC-vaccinated, CD4-deficient mice predominantly reacted to a 55-kDa PC antigen. These studies show promise for advances in CD4-independent vaccination against HIV-related pathogens.