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诱导针对CCR5趋化因子受体的抑制性抗体及其在预防猕猴感染猴免疫缺陷病毒中的互补作用。

Induction of inhibitory antibodies to the CCR5 chemokine receptor and their complementary role in preventing SIV infection in macaques.

作者信息

Lehner T, Wang Y, Doyle C, Tao L, Bergmeier L A, Mitchell E, Bogers W M, Heeney J, Kelly C G

机构信息

Department of Immunobiology Guy's King's and St. Thomas' Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, GB.

出版信息

Eur J Immunol. 1999 Aug;29(8):2427-35. doi: 10.1002/(SICI)1521-4141(199908)29:08<2427::AID-IMMU2427>3.0.CO;2-5.

DOI:10.1002/(SICI)1521-4141(199908)29:08<2427::AID-IMMU2427>3.0.CO;2-5
PMID:10458756
Abstract

The seven-transmembrane G-protein-linked CCR5 molecule functions as a major coreceptor for HIV or simian immunodeficiency virus (SIV) infection. Antibodies to CCR5 were studied in rhesus macaques immunized with SIV grown in human CD4(+) T cells. These macaques were completely protected against i.v. challenge with live SIV. Sera from the protected macaques showed significantly greater inhibition of SIV replication (p < 0.001) and macrophage inflammatory protein-1beta-generated CCR5-dependent chemotaxis (p < 0.01) than sera from unprotected macaques, in the absence of significant neutralizing antibodies to SIV. These two functional assays demonstrate serum antibodies to the CCR5 receptors which were specifically inhibited by CCR5-transfected HEK-293 cells. We postulate that anti-CCR5 antibodies may be complementary to beta-chemokines in blocking CCR5 coreceptors to HIV or SIV binding and fusion of CD4(+) cells.

摘要

七跨膜G蛋白偶联的CCR5分子是HIV或猿猴免疫缺陷病毒(SIV)感染的主要共受体。在用在人CD4(+) T细胞中培养的SIV免疫的恒河猴中研究了CCR5抗体。这些恒河猴完全受到保护,免受活SIV的静脉内攻击。在没有针对SIV的显著中和抗体的情况下,来自受保护恒河猴的血清对SIV复制的抑制作用(p < 0.001)和巨噬细胞炎性蛋白-1β产生的CCR5依赖性趋化作用(p < 0.01)显著大于来自未受保护恒河猴的血清。这两种功能测定证明了针对CCR5受体的血清抗体,其被CCR5转染的HEK-293细胞特异性抑制。我们推测抗CCR5抗体在阻断CCR5共受体与HIV或SIV结合以及CD4(+)细胞融合方面可能与β趋化因子互补。

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