Bouhlal Hicham, Latry Vanessa, Requena Mary, Aubry Sylvie, Kaveri Srinivas V, Kazatchkine Michel D, Belec Laurent, Hocini Hakim
Institut Nationale de la Santé et de la Recherche Médicale (INSERM) U743, Equipe d'Immunité et Biothérapies Muqueuses et Université René Descartes Paris V, Institut Biomédical des Cordeliers, France.
J Immunol. 2005 Jun 1;174(11):7202-9. doi: 10.4049/jimmunol.174.11.7202.
In the present study, we demonstrate that breast milk of 66% and 83% of HIV-seronegative and seropositive women, respectively, contains natural Abs of the secretory IgA and IgG isotypes directed against the CCR5 coreceptor for R5-tropic strains of HIV-1. Abs to CCR5 were affinity purified on a matrix to which a synthetic peptide corresponding to the second extracellular loop of CCR5 had been coupled. The purified Abs bound to the CCR5 peptide in a dose-dependent fashion and to both native CCR5 expressed by Chinese hamster ovary cells transfected with CCR5 gene, macrophages, and immature dendritic cells. Although the avidity differed, the amount of anti-CCR5 Abs did not significantly differ between breast milk of HIV-seropositive and -seronegative women. Purified anti-CCR5 Abs inhibited up to 75% infection of macrophages and dendritic cells with HIV(BaL) and HIV(JR-CSF). Our observations provide evidence for a role of natural Abs to CCR5 in breast milk in controlling transmissibility of HIV through breastfeeding.
在本研究中，我们证明，分别有66%的HIV血清阴性女性和83%的HIV血清阳性女性的母乳中含有针对HIV-1 R5嗜性毒株的共受体CCR5的分泌型IgA和IgG同种型天然抗体。抗CCR5抗体在一种基质上进行亲和纯化，该基质偶联了与CCR5第二个细胞外环对应的合成肽。纯化后的抗体以剂量依赖方式与CCR5肽结合，并与用CCR5基因转染的中国仓鼠卵巢细胞、巨噬细胞和未成熟树突状细胞表达的天然CCR5结合。尽管亲和力有所不同，但HIV血清阳性和血清阴性女性母乳中的抗CCR5抗体量并无显著差异。纯化后的抗CCR5抗体可抑制HIV(BaL)和HIV(JR-CSF)对巨噬细胞和树突状细胞高达75%的感染。我们的观察结果为母乳中抗CCR5天然抗体在控制HIV通过母乳喂养传播方面的作用提供了证据。
