Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release
Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release
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DOI：
10.1046/j.1365-2567.2003.01569.x
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发表时间：
2003-02-01
期刊：
影响因子：
6.4
通讯作者：
Stevens, E
中科院分区：
文献类型：
--
作者：
Arredouani, M;Matthijs, P;Stevens, E
T辅助细胞1型（Th 1）和2型（Th 2）免疫应答的特征在于T细胞活化后细胞因子表达的不同模式。Th 1与Th 2细胞比例的改变是对病毒和寄生虫感染、过敏、抗肿瘤反应和自身免疫的易感性的重要决定因素。在这项工作中，我们带来了新的证据结合珠蛋白（Hp），一个积极的急性期蛋白，对T淋巴细胞功能的影响。我们发现Hp特异性地与静息和活化的CD 4（+）和CD 8（+）T细胞相互作用。这种特异性结合导致对诱导的T细胞增殖的强烈抑制。此外，Hp在体外对Th 2细胞因子释放表现出强烈的抑制作用，而干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）的产生在高Hp剂量下仅受到轻微抑制。结果，如在Hp缺陷小鼠中所证明的，Hp的存在促进体内Th 1活化超过Th 2活化。抗CD 3单克隆抗体注射确实导致Hp（-/-）小鼠中主要产生IL-4，而Hp（+/+）小鼠中主要产生IFN-γ。我们的结论是，幽门螺杆菌发挥调节作用的Th 1/Th 2平衡，通过促进一个占主导地位的Th 1细胞反应。这表明了急性期蛋白在平衡免疫反应中的作用。
T helper cell type 1 (Th1) and type 2 (Th2) immune responses are characterized by a different pattern of cytokine expression following T-cell activation. Alterations of the ratio of Th1 to Th2 cells are important determinants of susceptibility to viral and parasitic infections, allergies, antitumour responses, and autoimmunity. In this work we bring new evidence for an effect of haptoglobin (Hp), a positive acute-phase protein, on T-lymphocyte functions. We show that Hp specifically interacts with both resting and activated CD4(+) and CD8(+) T cells. This specific binding results in a strong suppression of induced T-cell proliferation. In addition, Hp exhibits a strong in vitro inhibitory effect on Th2 cytokine release, while the production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) is only slightly inhibited at high Hp doses. As a result, the presence of Hp promotes Th1 activation over Th2 activation in vivo as evidenced in Hp-deficient mice. Anti-CD3 monoclonal antibody injection indeed resulted in predominant IL-4 production in Hp(-/-) mice, in contrast to predominant IFN-gamma production in Hp(+/+) mice. We conclude that Hp plays a modulating role on the Th1/Th2 balance by promoting a dominant Th1 cellular response. This points to a role of acute-phase proteins in balancing immune responses.