IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques
IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques
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DOI：
10.1016/s0020-7519(01)00355-1
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发表时间：
2002-05-01
影响因子：
4
通讯作者：
Weiner, DB
中科院分区：
文献类型：
--
作者：
Boyer, JD;Nath, B;Weiner, DB
人们普遍认为，Th 1型CD 4应答对于增强CD 8免疫和控制HIV-1感染至关重要。Th 2型反应，如在慢性寄生虫感染中可能看到的反应，会牺牲细胞免疫力，从而以宿主为代价使病毒受益。然而，在灵长类动物模型系统中，几乎没有直接检验这一假设。因此，使用猴免疫缺陷病毒（SIV）感染的恒河猴模型来研究用表达SIV的DNA构建体免疫和与IL-4共注射对SIV特异性免疫应答、淋巴细胞计数以及对病毒载量的影响。IL-4是一种Th 2型细胞因子，可增强抗体产生并抑制CD 4 Th 1表型。恒河猴用10AID 50的SrVmac 239感染，并在感染后9周用9-[2-（膦酰甲氧基）丙基]腺嘌呤（PMPA）处理。在PMPA治疗期间，用表达SIV蛋白env、rev、gag和pol的质粒免疫动物。此外，用编码IL-4基因的构建体免疫动物。IL-4共免疫增加了该组中的中和抗体滴度。重要的是，尽管中和抗体滴度较高，但用IL-4表达质粒接种的动物中的病毒载量在免疫方案期间增加。此外，PMPA治疗前中和抗体与病毒设定点无关，但PMPA治疗后病毒载量与抗体滴度相关。病毒载量抑制后抗体滴度降低。重要的是，在不存在IL-4的情况下接种疫苗保护了CD 4水平而不增加病毒载量。这些数据支持这样的假设，即对Th 2通路的不适当的免疫偏好最终会促进疾病的进展。(C)2002年澳大利亚寄生虫学会由爱思唯尔科技有限公司出版。保留所有权利。
It is widely believed that a Th 1 type CD4 response is critical for enhancement of CD8 immunity and for controlling HIV-1 infection. Th2 type responses, such as what might be seen in a chronic parasitic infection, would sacrifice cellular immunity and thus benefit the virus at the expense of the host. However, there has been little direct examination of the hypothesis in a primate model system. Accordingly, the simian immunodeficiency virus (SIV) infected rhesus macaque model was used to investigate the impact of immunisation with SIV expressing DNA constructs and co-injection with IL-4 on the SIV specific immunological responses, lymphocyte cell counts, as well as the impact on viral load. IL-4 is a Th2 type cytokine, which enhances antibody production and inhibits a CD4 Th1 phenotype. Rhesus macaques were infected with 10 AID50 of SrVmac239 and treated with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) 9 weeks post-infection. During PMPA treatment, animals were immunised with plasmids that expressed the SIV proteins, env, rev, gag and pol. In addition, they were immunised with a construct that encoded the gene for IL-4. IL-4 co-immunisation increased the neutralizing antibody titres in this group. Importantly, the viral loads in animals vaccinated with IL-4 expressing plasmid increased during the immunisation regimens despite the higher neutralizing antibody titres. In addition, neutralizing antibodies did not correlate with viral set point prior to PMPA treatment, however, there was a correlation between viral loads and antibody titres following the treatment with PMPA. Antibody titres decreased following the suppression of viral load. Importantly, vaccination in the absence of IL-4 protected CD4 levels without increasing viral load. The data support the hypothesis that inappropriate immune bias toward a Th2 pathway would ultimately enhance disease progression. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.