Cytokines and impaired CD8(+) CTL activity among elderly persons and the enhancing effect of IL-12
Cytokines and impaired CD8(+) CTL activity among elderly persons and the enhancing effect of IL-12
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DOI：
10.1016/s0047-6374(96)01855-6
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发表时间：
1997-03-01
影响因子：
5.3
通讯作者：
Couch, RB
中科院分区：
文献类型：
--
作者：
Mbawuike, IN;Acuna, CL;Couch, RB
我们之前已经证明，与年轻人相比，约 70% 的老年人表现出针对流感病毒的细胞毒性 T 淋巴细胞 (CD8(+) CTL) 反应不足。由于IFN-γ（一种Th1细胞因子）和IL-4（一种Th2细胞因子）分别刺激和抑制CD8（+）CTL反应，因此研究了它们在与年龄相关的CTL缺陷中的作用。来自年轻人（34+/-5岁）和老年受试者（71+/-1岁）的淋巴细胞在体外用甲型/H3N2、甲型/H1N1或乙型流感病毒刺激6-7天。老年人针对病毒感染的自体靶细胞的CD8(+) CTL活性显着低于年轻受试者(P < 0.01)。流感病毒刺激后，第 3 天，两个年龄组的 IL-4 产量相似，但第 6 天，老年人的 IL-4 产量显着更高（P < 0.05）。相比之下，在这两天中，老年人的 T 细胞产生的 IFN-γ 明显低于年轻人（P < 0.05）。用重组人 IL-12（一种刺激 Th1 细胞因子的关键细胞因子）处理年轻人和老年人的 T 细胞，导致 CD8(+) CTL 活性和 IFN-γ 产生以剂量依赖性方式增强（P < 0.01）。 IL-12 依赖性的 CTL 活性增强并不总是被抗 IFN-γ 抗体治疗所消除。这些结果表明，老年人中流感病毒特异性 CTL 活性的缺陷可归因于 Th1 细胞因子向 Th2 细胞因子产生的转换。 IL-12 免疫疗法可能是纠正老年人 CD8(+) CTL 缺陷和细胞因子失衡的有效方法。 (C) 1997 爱思唯尔科学爱尔兰有限公司
We have previously demonstrated that about 70% of elderly persons exhibit deficient cytotoxic T lymphocyte (CD8(+) CTL) responses against influenza viruses when compared to young persons. Since IFN-gamma, a Th1 cytokine and IL-4, a Th2 cytokine, stimulate and inhibit CD8(+) CTL responses respectively, their role(s) in the age-related CTL deficiency was investigated. Lymphocytes from young adults (34 +/- 5 years old) and elderly subjects (71 +/- I years old) were stimulated in vitro with influenza A/H3N2, A/H1N1 or influenza B virus for 6-7 days. The CD8(+) CTL activity against virus-infected autologous target cells was significantly lower among the elderly than the young subjects (P < 0.01). Following stimulation with influenza virus, IL-4 production in both age groups was similar on day 3 but significantly higher among elderly persons on day 6 (P < 0.05). In contrast, T cells from the elderly produced significantly lower IFN-gamma than did those from young persons on both days (P < 0.05). Treatment of T cells from young and elderly adults with recombinant human IL-12, a pivotal cytokine that stimulates Th1 cytokines, resulted in enhancement of CD8(+) CTL activity and IFN-gamma production in a dose dependent manner (P < 0.01). IL-12-dependent enhancement of CTL activity was not always abrogated by anti-IFN-gamma antibody treatment. These results suggest that deficient influenza virus-specific CTL activity among the elderly is attributable to a Th1 to Th2 cytokine production switch. Immunotherapy with IL-12 could represent a useful approach to correct the CD8(+) CTL deficiency and cytokine imbalance among elderly humans. (C) 1997 Elsevier Science Ireland Ltd.