Differences in components at delayed-type hypersensitivity reaction sites in mice immunized with either a protective or a nonprotective immunogen of Cryptococcus neoformans.
Differences in components at delayed-type hypersensitivity reaction sites in mice immunized with either a protective or a nonprotective immunogen of Cryptococcus neoformans.
复制标题
用新型隐球菌的保护性或非保护性免疫原免疫的小鼠迟发型超敏反应部位的成分差异。
DOI：
10.1128/iai.70.2.591-600.2002
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发表时间：
2002
影响因子：
3.1
通讯作者：
Murphy,JuneannW
中科院分区：
文献类型：
--
作者：
Nichols,KasieL;Bauman,SeanK;Schafer,FreddaB;Murphy,JuneannW
细胞免疫是新生隐球菌的主要保护机制。延迟的肿胀反应，即，迟发型超敏反应（DTH）作为检测对抗原的细胞介导的免疫（CMI）反应的手段。我们以前已经发现，在小鼠中存在抗隐球菌DTH反应并不总是表明对隐球菌感染的保护。使用一种诱导保护性抗隐球菌CMI反应的免疫原和一种诱导非保护性反应的免疫原，我们已经表明用保护性免疫原免疫的小鼠经历典型的DTH反应，其特征在于单核细胞和中性粒细胞浸润以及γ干扰素和NO的存在。用非保护性免疫原免疫导致主要中性粒细胞的流入和在DTH反应位点产生肿瘤坏死因子α（TNF-α）。即使当通过阻断给予非保护性免疫原的小鼠T细胞上的下调因子CTLA-4（CD 152）来增强抗隐球菌DTH反应时，浸润DTH反应部位的主要白细胞群体是中性粒细胞。尽管在用非保护性免疫原免疫的小鼠中，DTH反应部位的TNF-α增加，但TNF-α不太可能激活中性粒细胞，因为中性粒细胞上TNF受体的密度降低至低于对照水平。DTH反应性和保护的解偶联已在其他感染性疾病模型中得到证实;然而，其机制与我们的模型不同。这些发现强调了定义各种免疫原反应中发生的级联事件以及建立保护和DTH反应之间关系的重要性。
Cell-mediated immunity is the major protective mechanism againstCryptococcus neoformans. Delayed swelling reactions, i.e., delayed-type hypersensitivity (DTH), in response to an intradermal injection of specific antigen are used as a means of detecting a cell-mediated immune (CMI) response to the antigen. We have found previously that the presence of an anticryptococcal DTH response in mice is not always indicative of protection against a cryptococcal infection. Using one immunogen that induces a protective anticryptococcal CMI response and one that induces a nonprotective response, we have shown that mice immunized with the protective immunogen undergo a classical DTH response characterized by mononuclear cell and neutrophil infiltrates and the presence of gamma interferon and NO. In contrast, immunization with the nonprotective immunogen results in an influx of primarily neutrophils and production of tumor necrosis factor alpha (TNF-α) at the DTH reaction site. Even when the anticryptococcal DTH response was augmented by blocking the down-regulator, CTLA-4 (CD152), on T cells in the mice given the nonprotective immunogen, the main leukocyte population infiltrating the DTH reaction site is the neutrophil. Although TNF-α is increased at the DTH reaction site in mice immunized with the nonprotective immunogen, it is unlikely that TNF-α activates the neutrophils, because the density of TNF receptors on the neutrophils is reduced below control levels. Uncoupling of DTH reactivity and protection has been demonstrated in other infectious-disease models; however, the mechanisms differ from our model. These findings stress the importance of defining the cascade of events occurring in response to various immunogens and establishing the relationships between protection and DTH reactions.