Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major
Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major
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DOI：
10.1038/nm1592
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发表时间：
2007-07-01
期刊：
影响因子：
82.9
通讯作者：
Seder, Robert A.
中科院分区：
文献类型：
--
作者：
Darrah, Patricia A.;Patel, Dipti T.;Seder, Robert A.
CD 4（+）T细胞通过产生特异性细胞因子在介导针对多种病原体的保护中具有至关重要的作用。然而，CD 4（+）T细胞细胞因子应答的实质异质性限制了确定疫苗接种后保护的免疫相关性的能力。在这里，使用多参数流式细胞术来评估免疫后的免疫反应，我们表明，对利什曼原虫感染小鼠的保护程度是由CD 4（+）T细胞同时产生干扰素-γ，白细胞介素-2和肿瘤坏死因子的频率预测。值得注意的是，由所有测试的疫苗产生的多功能效应细胞在产生大量干扰素-γ的能力方面是独特的。这些数据表明，CD 4（+）T细胞细胞因子应答的质量可能是疫苗是否具有保护性的关键决定因素，并可能为基于T辅助1型（T（H）1）细胞的疫苗提供新的和有用的前瞻性免疫保护相关性。
CD4(+) T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4(+) T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4(+) T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4(+) T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (T(H)1) cells.