Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France.
J Leukoc Biol. 2010 Apr;87(4):645-53. doi: 10.1189/jlb.1009684. Epub 2010 Jan 22.
IL-12 enhances protective responses against HIV replication. Its production after in vitro stimulation is defective in chronic HIV infection, but higher responses can be found. IL-23 shares the p40 chain and some properties with IL-12 and enhances Th17 responses, but its role in HIV infection is unknown. The production of IL-12 and IL-23 and the respective contribution of monocytes and myeloid conventional DC (cDCs) during primary HIV infection were determined. Sixteen patients included in the French PRIMO-ANRS Cohort without antiretroviral treatment were followed prospectively and compared with uninfected donors. Intracellular p40 expression by monocytes and cDCs, analyzed by flow cytometry, was transiently increased in monocytes and cDCs in response to LPS and more consistently, in monocytes in response to LPS + IFN-gamma. IL-23 production, measured by ELISA after PBMC stimulation, was induced by LPS in strong correlation with VLs. IL-12p70 production required the addition of IFN-gamma and was transiently increased in patients compared with controls in correlation with VLs, whereas IL-23 was increased sustainedly. Therefore, an apparent domination of IL-23 over IL-12 responses occurred throughout primary HIV infection, and a potential restoration of IL-12 responses might be expected from a treatment mimicking activated T cell signals.
白细胞介素 12 增强了针对 HIV 复制的保护反应。在慢性 HIV 感染中,其体外刺激后的产生存在缺陷,但可以发现更高的反应。白细胞介素 23 与白细胞介素 12 共享 p40 链和一些特性,并增强 Th17 反应,但它在 HIV 感染中的作用尚不清楚。本研究旨在确定原发性 HIV 感染期间白细胞介素 12 和白细胞介素 23 的产生及其在单核细胞和髓系常规树突状细胞 (cDCs) 中的各自贡献。前瞻性随访了来自法国 PRIMO-ANRS 队列的 16 名未接受抗逆转录病毒治疗的患者,并与未感染的供体进行了比较。通过流式细胞术分析,细胞内 p40 表达在单核细胞和 cDCs 中对 LPS 呈短暂增加,而在单核细胞中对 LPS+IFN-γ的反应更为一致。通过 PBMC 刺激后 ELISA 测量的 IL-23 产生与 VLs 呈强相关,由 LPS 诱导。IL-12p70 的产生需要 IFN-γ的加入,并在患者中与对照组相比呈短暂增加,与 VLs 相关,而 IL-23 则持续增加。因此,在原发性 HIV 感染期间,IL-23 对 IL-12 反应的明显优势,以及从模拟激活 T 细胞信号的治疗中可能预期的 IL-12 反应的恢复。