During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion
During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion
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DOI：
10.4049/jimmunol.175.3.1665
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发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Borst, J
中科院分区：
文献类型：
--
作者：
Hendriks, J;Xiao, YL;Borst, J
独立的研究表明，CD 27、4-1BB和OX 40都可以促进活化的CD 8（+）T细胞的存活。因此，我们在一个生理相关的模型系统中比较了它们对CD 8+记忆T细胞形成和反应性的影响。选择性缺乏一种或两种受体输入的重组小鼠用流感病毒鼻内攻击，并在引发和效应位点定量免疫显性病毒特异性CD 8 + T细胞应答。初次感染后，CD 27和（在较小程度上）4-1BB对引流淋巴结和肺中CD 8（+）病毒特异性T细胞的积累起到了非冗余作用，而OX 40则没有影响。有趣的是，在记忆反应中，病毒特异性CD 8 + T细胞在脾和肺中的积累严重依赖于所有三种受体系统。这可以通过两个观察结果来解释：1）CD 27、4-1BB和OX 40共同负责产生相同的记忆CD 8 + T细胞库; 2）CD 27、4-1BB和OX 40共同决定了二次扩增的程度，如具有标准数量的记忆细胞的过继转移所示。令人惊讶的是，野生型CD 8（+）记忆T细胞在致敏的OX 40配体或4-1BB配体缺陷小鼠中正常扩增。然而，当在OX 40配体或4-1BB配体缺陷小鼠中产生野生型记忆细胞时，其二次扩增受损。这提供了新的概念，即在引发期间通过OX 40和4-1BB配体刺激CD 8（+）T细胞使其具有二次扩增的能力。我们的数据表明，树突状细胞和/或B细胞上的配体可能对此至关重要。
Independent studies have shown that CD27, 4-1BB, and OX40 can all promote survival of activated CD8(+) T cells. We have therefore compared their impact on CD8+ memory T cell formation and responsiveness within one, physiologically relevant model system. Recombinant mice, selectively lacking input of one or two receptors, were challenged intranasally with influenza virus, and the immunodominant virus-specific CD8+ T cell response was quantified at priming and effector sites. Upon primary infection, CD27 and (to a lesser extent) 4-1BB made nonredundant contributions to accumulation of CD8(+) virus-specific T cells in draining lymph nodes and lung, while OX40 had no effect. Interestingly though, in the memory response, accumulation of virus-specific CD8+ T cells in spleen and lung critically depended on all three receptor systems. This was explained by two observations: 1) CD27, 4-1BB, and OX40 were collectively responsible for generation of the same memory CD8+ T cell pool; 2) CD27, 4-1BB, and OX40 collectively determined the extent of secondary expansion, as shown by adoptive transfers with standardized numbers of memory cells. Surprisingly, wild-type CD8(+) memory T cells expanded normally in primed OX40 ligand- or 4-1BB ligand-deficient mice. However, when wild-type memory cells were generated in OX40 ligand- or 4-1BB ligand-deficient mice, their secondary expansion was impaired. This provides the novel concept that stimulation of CD8(+) T cells by OX40 and 4-1BB ligand during priming imprints into them the capacity for secondary expansion. Our data argue that ligand on dendritic cells and/or B cells may be critical for this.