Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection
Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection
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DOI：
10.4049/jimmunol.168.8.3777
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发表时间：
2002-04-15
影响因子：
4.4
通讯作者：
Watts, TH
中科院分区：
文献类型：
--
作者：
Bertram, EM;Lau, P;Watts, TH
在这份报告中，我们证明，CD 28（-/-）小鼠在D-b/NP 366 -374特异性CD 8 T细胞对流感病毒感染的初始扩增中严重受损，而4-1BB配体（4-1BBL）（-/-）小鼠在对流感病毒的初始T细胞扩增中没有表现出缺陷。相比之下，4-1BBL（-/-）小鼠在初次应答后期显示Db/NP 366 -374特异性T细胞减少。在用流感病毒进行二次攻击后，与野生型小鼠相比，4-1BBL（-/-）小鼠显示D-b/NP 366 -374特异性T细胞的数量减少，使得体内二次应答期间的CD 8 T细胞扩增水平降低至初次应答的水平，伴随着CTL效应子功能的降低。相比之下，抗体反应，以及继发性CD 4 T细胞反应，流感是不受4-1BBL缺陷。因此，CD 28对于初始T细胞扩增至关重要，而4-1BB/4-1BBL信号传导在应答中影响T细胞数量，并且对于记忆性CD 8 T细胞库的存活和/或应答性至关重要。
In this report, we demonstrate that CD28(-/-) mice are severely impaired in the initial expansion of D-b/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)(-/-) mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL(-/-) mice show a decrease in Db/NP366-374-specific T cells late in the primary response. Upon secondary challenge with influenza virus, 4-1BBL(-/-) mice show a decrease in the number of D-b/NP366-374-specific T cells compared to wild-type mice such that the level of the CD8 T cell expansion during the in vivo secondary response is reduced to the level of a primary response, with concomitant reduction of CTL effector function. In contrast, Ab responses, as well as secondary CD4 T cell responses, to influenza are unaffected by 4-1BBL deficiency. Thus, CD28 is critical for initial T cell expansion, whereas 4-1BB/4-1BBL signaling affects T cell numbers much later in the response and is essential for the survival and/or responsiveness of the memory CD8 T cell pool.