Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression.
Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression.
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DOI：
10.1182/blood-2005-06-2463
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发表时间：
2006-06
期刊：
影响因子：
20.3
通讯作者：
C. Pastori;B. Weiser;C. Barassi;C. Uberti-Foppa;S. Ghezzi;R. Longhi;G. Calori;H. Burger;K. Kemal;G. Poli;A. Lazzarin;L. Lopalco
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文献类型：
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作者：
C. Pastori;B. Weiser;C. Barassi;C. Uberti-Foppa;S. Ghezzi;R. Longhi;G. Calori;H. Burger;K. Kemal;G. Poli;A. Lazzarin;L. Lopalco
暴露于HIV-1不一定导致感染和疾病进展，因此表明可以实现病毒感染的控制。在HIV暴露但未感染的受试者（ESN）中检测到CCR 5抗体;因此，这些抗体可能参与HIV保护。为了评估抗CCR 5抗体是否也有助于减缓HIV疾病进展，我们在497名受试者中搜索了抗CCR 5抗体，包括85名长期无进展者（LTNP），70名进展者，135名接受高效抗逆转录病毒治疗（HAART）的HIV（+）患者和207名血清阴性供体。我们在LTNP的一部分（23.5%）中发现了抗CCR 5抗体，但在其他研究人群中没有发现（P <0.001）。这些抗体识别CCR 5的第一个膜外环内的构象表位，并且它们诱导T淋巴细胞表面上的CCR 5稳定且持久的下调，这抑制了HIV进入。此外，来自具有抗CCR 5抗体的LTNP的CD 4（+）淋巴细胞对HIV-1的R5株具有抗性。随访研究显示，一些受试者发生抗CCR 5抗体的丢失，这种丢失与疾病进展显著相关，而保留抗CCR 5抗体的受试者保持其LTNP状态。抗CCR 5抗体的诱导可能与疫苗设计和治疗相关。
Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV(+) patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs(23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4(+) lymphocytes from LTNPs having anti-CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics.