Defective T cell priming associated with aging can be rescued by signaling through 4-1BB (CD137)
Defective T cell priming associated with aging can be rescued by signaling through 4-1BB (CD137)
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DOI：
10.4049/jimmunol.169.9.5005
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发表时间：
2002-11-01
影响因子：
4.4
通讯作者：
Croft, M
中科院分区：
文献类型：
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作者：
Bansal-Pakala, P;Croft, M
衰老与对感染因子的易感性增加有关，并与免疫应答能力降低有关。据推测，主要缺陷与老化的T细胞在遇到Ag后增殖和存活的能力降低有关。这与年轻人中与T细胞耐受相关的表型相似。在这项研究中，我们确定了靶向4-1BB（CD 137），TNFR家族的一个成员，参与提供扩展和生存信号的T细胞，可以挽救有缺陷的启动在老年和耐受的动物。体内注射的针对4-1BB的激动剂Ab能够防止幼年小鼠中的CD 4 T细胞对可溶性肽的耐受。此外，抗4-1BBB挽救了年轻宿主中对肽Ag应答的老年TCR转基因CD 4 T细胞的缺陷性引发，同样重要的是，抗4-1BB完全恢复了非转基因老年小鼠中对蛋白Ag的T细胞引发。这些研究表明，4-1BB，和潜在的TNFR家族的其他共刺激成员，是治疗的目标，旨在增强老年免疫功能低下的个人弱T细胞反应。
Aging is associated with an increased susceptibility to infectious agents and correlates with a decreased ability to mount an immune response. It has been postulated that the major defect is related to a reduced capacity of an aged T cell to proliferate and to survive after encounter with Ag. This is similar to the phenotype associated with T cell tolerance in young adults. In this study, we determined whether targeting 4-1BB (CD137), a member of the TNFR family implicated in providing expansion and survival signals to T cells, can rescue defective priming in aged and tolerized animals. Agonist Abs to 4-1BB injected in vivo were capable of preventing CD4 T cell tolerance to soluble peptide in young mice. Moreover, anti-4-1BBB rescued defective priming of aged TCR transgenic CD4 T cells responding to peptide Ag in a young host, and as importantly, anti-4-1BB completely restored T cell priming to protein Ag in nontransgenic aged mice. These studies demonstrate that 4-1BB, and potentially other costimulatory members of the TNFR family, are targets for therapies aimed at augmenting weak T cell responses in elderly immunocompromised individuals.