The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers - A review and hypothesis
The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers - A review and hypothesis
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DOI：
10.1023/b:viru.0000012260.32578.72
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发表时间：
2004-01-01
期刊：
影响因子：
1.6
通讯作者：
Becker, Y
中科院分区：
文献类型：
--
作者：
Becker, Y
人类的HIV-1感染诱导早期细胞免疫应答，以细胞毒性T细胞（CTL）应答与病毒蛋白反应，该细胞毒性T细胞应答不能抑制病毒复制和病毒传播。很明显，疾病的进展导致免疫系统的慢性变化，其中IgE抗体的逐渐增加是其特征之一。当HIV-1开始流行时，IgE含量的逐渐增加与艾滋病之间的关系尚不清楚，但后来它成为疾病预后的标志。对辅助性T细胞1（Th 1）和辅助性T细胞2（Th 2）的认识的进展揭示了Th 1细胞产生刺激CTL增殖的细胞因子。Th 2细胞产生细胞因子，其负责激活健康人的体液免疫应答。对Th 1和Th 2细胞因子合成的研究揭示了HIV-1感染者的畸变。Clerici和Shearer提出了一种假说（1993），其中Th 1细胞活性下降而Th 2活性增加（Th 1. Th 2开关假说）。事实上，关于这一假设的实验最终支持了这样一个前提，即开关涉及细胞因子平衡的关键变化，这导致了艾滋病的收缩。然而，研究界仍然必须弄清楚为什么这样的Th 1。Th 2开关发生在感染者身上，以及如何逆转。目前的审查指出，一个类似的Th 1. Th 2开关构成过敏人群对环境过敏原的反应。暴露于过敏原的HIV-1患者和过敏人群的反应是Th 2细胞因子和IgE的合成增加，同时Th 1细胞因子减少。对变应原诱导的Th 2细胞的研究表明，Th 2细胞因子IL-4诱导B细胞合成IgE，细胞因子IL-5是嗜酸性粒细胞增多的诱导物，就像在HIV-1感染中一样。HIV-1感染和过敏之间的区别是IL-4诱导T细胞合成HIV-1辅助受体CXCR 4的能力，CXCR 4从复制病毒中选择合胞体诱导（SI）病毒，一种快速复制的变异病毒。本假说暗示病毒蛋白在诱导Th 2细胞因子的合成。这表明，在病毒蛋白，过敏原样结构域可能是负责激活Th 2细胞因子的合成。基于人类对过敏原和HIV-1的反应的类比，提出了以下假设：（a）通过基因工程从病毒基因中去除过敏原样结构域可能为疫苗开发提供病毒蛋白。(b)用IL-4受体抑制剂治疗过敏性患者的尝试表明，“Th 2-> Th 1逆转”构成了抑制Th 2细胞因子和诱导抗病毒Th 1应答复苏的可能途径。
The HIV-1 infection in humans induces an early cellular immune response to react to the viral proteins with a cytotoxic T cell (CTL) response that fails to inhibit virus replication and the spread of the virus. It became evident that the progression of the disease causes chronic changes to the immune system of which a gradual increase in IgE antibodies is one of its features. When the HIV-1 epidemic began, the relation between the gradual increase in IgE content and AIDS was not understood, but later it became a marker for disease prognosis. The advances in the knowledge on T helper 1 (Th1) and T helper 2 (Th2) cells revealed that Th1 cells produce cytokines that stimulate the proliferation of CTLs. Th2 cells produce cytokines that are responsible for the activation of the humoral immune response in healthy people. Studies on both Th1 and Th2 cytokine synthesis revealed an aberration in HIV-1 infected people. Clerici and Shearer presented a hypothesis ( 1993) whereby Th1 cell activity declines and Th2 activity increases ( the Th1. Th2 switch hypothesis) in HIV-1 infected people. In fact, experiments concerning this hypothesis ultimately supported the premise that the switch involves a critical change in the cytokine balance, which leads to the contraction of AIDS. However, the research community must still discern why such a Th1. Th2 switch takes place in infected people and how it can be reversed. The present review points to the fact that a similar Th1. Th2 switch constitutes the response of allergic people to environmental allergens. HIV-1 patients and allergic people that are exposed to allergens respond with an increased synthesis of Th2 cytokines and IgE, together with a decrease in Th1 cytokines. The studies on allergen-induced Th2 cells revealed that the Th2 cytokine IL-4 induces B cells to synthesize IgE, and cytokine IL-5 is the inducer of eosinophilia, just as in HIV-1 infection. The difference between the HIV-1 infection and allergies is the ability of IL-4 to induce the synthesis in T cells of the HIV-1 coreceptor CXCR4 that selects from the replicating virus a syncytium-inducing ( SI) virus, a variant virus that replicates rapidly. The present hypothesis implicates the viral proteins in the induction of Th2 cytokine synthesis. This suggests that in viral proteins, allergen-like domains may be responsible for the activation of Th2 cytokine synthesis. Based on the analogy of the responses of humans to allergens and HIV-1, the following hypotheses is suggested: ( a) Removal of allergen-like domains from viral genes by genetic engineering may provide viral proteins for vaccine development. (b) Attempts to treat allergic patients with IL-4 receptor inhibitors suggests that the "Th2 --> Th1 Reversion'' constitutes a possible approach to inhibiting the Th2 cytokines and inducing a revival of the anti-viral Th1 response.