Marone G, Florio G, Petraroli A, de Paulis A
Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy.
J Allergy Clin Immunol. 2001 Jan;107(1):22-30. doi: 10.1067/mai.2001.111589.
Serum IgE levels are increased in adults and children with HIV-1 infection and could be a marker of poor prognosis. Allergic reactions and adverse reactions to drugs are also increased in HIV-1-infected individuals. An imbalance between a T(H)1-like and a T(H)2-like cytokine profile has been documented in HIV-1 infection. We have found that HIV-1 gp120 from different clades is a potent stimulus for histamine and cytokine (IL-4 and IL-13) release from basophils. Gp120 acts as a viral superantigen, interacting with the V(H)3 region of IgE to induce mediator release from human Fc epsilon RI(+) cells. Human basophils and mast cells express the chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES. By interacting with the CCR3 receptor on Fc epsilon RI(+) cells, HIV-1 Tat protein is a potent chemoattractant for human basophils and lung mast cells. Tat protein also induced IL-4 and IL-13 release from basophils. Preincubation of basophils with Tat protein upregulated the surface expression of the CCR3 receptor. Extracellular Tat can influence the directional migration of human Fc epsilon RI(+) cells, the expression of chemokine receptor CCR3, and the release of T(H)2 cytokines. Because Tat protein is actively released by HIV-1-infected cells, our results indicate a novel mechanism by which Fc epsilon RI(+) cells are rendered more susceptible to infection with CCR3-tropic HIV-1 isolates; that is, two HIV-1 proteins, gp120 and Tat, trigger the release of cytokines critical for T(H)2 polarization from Fc epsilon RI(+) cells, and Tat upregulates beta-chemokine receptor CCR3 on these cells.
HIV-1感染的成人和儿童血清IgE水平升高，可能是预后不良的一个标志。HIV-1感染者对药物的过敏反应和不良反应也会增加。在HIV-1感染中，已证实存在类似T(H)1和类似T(H)2细胞因子谱之间的失衡。我们发现，来自不同分支的HIV-1 gp120是嗜碱性粒细胞释放组胺和细胞因子（IL-4和IL-13）的有效刺激物。Gp120作为一种病毒超抗原，与IgE的V(H)3区域相互作用，诱导人FcεRI(+)细胞释放介质。人嗜碱性粒细胞和肥大细胞表达趋化因子受体CCR3，该受体与趋化因子嗜酸性粒细胞趋化蛋白和RANTES结合。通过与FcεRI(+)细胞上CCR3受体相互作用，HIV-1 Tat蛋白是人类嗜碱性粒细胞和肺肥大细胞的有效化学引诱剂。Tat蛋白还诱导嗜碱性粒细胞释放IL-4和IL-13。嗜碱性粒细胞与Tat蛋白预孵育会上调CCR3受体的表面表达。细胞外Tat可影响人FcεRI(+)细胞的定向迁移、趋化因子受体CCR3的表达以及T(H)2细胞因子的释放。由于Tat蛋白由HIV-1感染细胞主动释放，我们的结果表明了一种新机制，通过该机制FcεRI(+)细胞对CCR3嗜性HIV-1分离株感染更易感；也就是说，两种HIV-1蛋白，gp120和Tat，触发FcεRI(+)细胞释放对T(H)2极化至关重要的细胞因子，并且Tat上调这些细胞上的β-趋化因子受体CCR3。
