T cell vaccination in mice with invasive pulmonary aspergillosis
T cell vaccination in mice with invasive pulmonary aspergillosis
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DOI：
10.4049/jimmunol.165.1.381
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发表时间：
2000-07-01
影响因子：
4.4
通讯作者：
Romani, L
中科院分区：
文献类型：
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作者：
Cenci, E;Mencacci, A;Romani, L
烟曲霉是一种机会致病真菌，可引起过敏性和非过敏性的多种气道疾病。在侵袭性肺曲霉病的小鼠模型中，抗性与肺部炎症病理学的降低和IL-12依赖性Th 1型反应性的发生相关，这两者都被IL-4损害。在本研究中，我们评估曲霉粗培养物滤液Ags和重组过敏原Asp f 2在侵袭性肺曲霉病小鼠中诱导保护性抗真菌反应的能力，类似于鼻腔暴露于活的A。烟曲霉分生孢子，用曲霉粗培养物滤液Ags处理免疫活性小鼠导致局部和外周保护性Th 1记忆应答的发展，该应答由产生IFN-γ和IL-2的Ag特异性CD 4（+）T细胞介导，能够在过继转移给幼稚受体后赋予保护。保护性Th 1应答不能在IFN-γ或IL-12缺乏的小鼠中观察到，并且不响应于Asp f 2而发生，相反，其引起高水平的抑制性IL-4的产生。结果表明，曲霉属Ags在感染过程中具有诱导Th 1和Th 2型反应的能力，这一发现表明了一种可能的机制，通过这种机制，感染小鼠的潜在保护性免疫应答受到抑制。然而，接种曲霉菌粗培养物滤液Ags后Th 1介导的抗性的发生表明真菌Ags的存在可用作针对侵袭性肺曲霉病的候选疫苗。
Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a murine model of invasive pulmonary aspergillosis, resistance is associated with a decreased lung inflammatory pathology and the occurrence of an IL-12-dependent Th1-type reactivity that are both impaired by IL-4, In the present study we assess the ability of Aspergillus crude culture filtrate Ags and the recombinant allergen Asp f 2 to induce protective antifungal responses in mice with invasive pulmonary aspergillosis, Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompetent mice with Aspergillus crude culture filtrate Ags resulted in the development of local and peripheral protective Th1 memory responses, mediated by Ag-specific CD4(+) T cells producing IFN-gamma and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 responses could not be observed in mice deficient of IFN-gamma or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high level production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which potentially protective immune responses are inhibited in mice with the infection. However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ags useful as a candidate vaccine against invasive pulmonary aspergillosis.