Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens
Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens
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DOI：
10.1086/377134
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发表时间：
2003-08-15
影响因子：
6.4
通讯作者：
Igietseme, JU
中科院分区：
文献类型：
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作者：
Moore, T;Ekworomadu, CO;Igietseme, JU
对包括衣原体在内的细胞内微生物的免疫主要由细胞介导的效应机制控制，然而，抗体的缺乏会导致微生物清除效率低下。我们研究了某些Fc受体功能促进快速诱导升高的辅助性T细胞1型(Th1)反应的假设，这有效地清除了衣原体。与FCR(+/+)小鼠相比，FCR(-/-)小鼠表现出衣原体特异性Th1细胞频率的延迟和降低。在体外，抗衣原体抗体可增加FCR(+/+)抗原提呈细胞的Th1激活率，但不能增加FCR(+/+)抗原提呈细胞的Th1激活率。FCR(-/-)树突状细胞和T细胞相关的IgG2a和IgA介导抗体增强Th1的激活。衣原体抗体复合体免疫可诱导高水平的保护性Th1反应。这些结果为在保护性免疫和疫苗评价中同时要求T细胞和体液免疫反应提供了机制基础。这些发现提供了一种宿主防御的范例，其中不同的效应器组件间接地发挥作用，使主要效应器机制最大化。
Immunity to intracellular microbial pathogens, including Chlamydia species, is controlled primarily by cell-mediated effector mechanisms, yet, the absence of antibodies results in inefficient microbial clearance. We investigated the hypothesis that certain Fc receptor functions promote the rapid induction of elevated T helper type 1 (Th1) response, which effectively clears chlamydiae. FcR(-/-) mice exhibited a delayed and reduced frequency of Chlamydia-specific Th1 cells, compared to FcR(+/+) mice. In vitro, antichlamydial antibodies increased the rate of Th1 activation by FcR(+/+) but not FcR(+/+) antigen-presenting cells. FcR(-/-) dendritic cells and the T cell-associated IgG2A and IgA mediate enhanced Th1 activation by antibodies. Immunization with chlamydia-antibody complexes induced elevated and protective Th1 response. These results provide a mechanistic basis for requiring both T cell and humoral immune responses in protective immunity and vaccine evaluation. Findings offer a paradigm in host defense wherein different effector components function indirectly to maximize the principal effector mechanism.