Genetic differences in the age-associated decrease in inducibility of natural killer cells by interferon-α/β

Genetic differences in the age-associated decrease in inducibility of natural killer cells by interferon-α/β
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DOI:
10.1016/s0047-6374(99)00091-3
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发表时间:
2000-01-10
影响因子:
5.3
通讯作者:
Murasko, DM
Murasko, DM
中科院分区:
医学3区
文献类型:
--
作者:
Plett, A;Murasko, DM

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在病毒感染和抗肿瘤活性中重要的自然杀伤(NK)细胞在老年小鼠中显示出降低的细胞毒性。这种与年龄相关的NK活性下降的机制尚未明确确定。我们评估了成年(6个月)和老年(22-26个月)C57 B1/6、Balb/c和(Balb/c x C57 B1/6)F-1小鼠在干扰素(IFN)-α/β刺激后脾细胞和外周血单核细胞中NK细胞毒性的变化。与成年小鼠相比,老年C57 B1/6和Balb/c小鼠具有显著降低的IFN-α/β刺激的NK细胞毒性。相反,成年和老年F-1小鼠在IFN-α/β诱导后显示出相似的NK细胞毒性。老年小鼠NK细胞对IFN-α/β诱导应答的能力降低不是由于需要增加IFN的量或更长时间的IFN治疗。此外,这种降低的应答似乎不是粘附细胞或T细胞的抑制活性的结果。虽然成年和老年小鼠中NK细胞(NK 1.1+)的百分比相似,但老年小鼠中NK细胞的(CD 8 + NK 1.1+)亚群显著增加。重要的是,CD 8 + NK 1.1+细胞的百分比与IFN-α/β处理后观察到的细胞毒性呈负相关。(C)2000由Elsevier Science爱尔兰有限公司出版。保留所有权利。
Natural killer (NK) cells, which are important in viral infections and anti-tumor activity, show reduced cytotoxicity in aged mice. The mechanism(s) for this age-related decline in NK activity has not been clearly established. We assessed changes in NK cytotoxicity in splenocytes and peripheral blood mononuclear cells after interferon (IFN)-alpha/beta stimulation in adult (6 months) and aged (22-26 months) C57B1/6, Balb/c, and (Balb/c x C57B1/6)F-1 mice. Aged C57B1/6 and Balb/c mice had a significantly reduced IFN-alpha/beta-stimulated NK cytotoxicity compared to adult mice. In contrast, adult and aged F-1 mice showed similar NK cytotoxicity after IFN-alpha/beta induction. The decreased ability of NK cells of aged mice to respond to induction by IFN-alpha/beta was not due to a requirement for an increased amount of IFN or for a longer period of treatment with IFN. Further, this decreased response did not appear to be the result of suppressive activity of adherent cells or T cells. While the percentage of NK cells (NK1.1 +) was similar in adult and aged mice, the (CD8 + NK1.1 +) subset of NK cells was significantly increased in aged mice. Importantly, the percentage of CD8+NK1.1+ cells was inversely related to the cytotoxicity observed after IFN-alpha/beta treatment. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.