Background: During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%–30% of treated patients show a discordant response to combined antiretroviral therapy. Myeloid-derived suppressor cells (MDSC) are expanded in HIV+ patients; to better understand the role of MDSC on CD4 T-cell recovery, we evaluated the frequency of MDSC in HIV+ patients under combined antiretroviral therapy and its association with immunologic response. Methods: We enrolled 60 HIV+ patients, including complete responders (R, n = 44), virologic nonresponders (VNR, n = 5), and immunologic nonresponders (INR, n = 11). The frequency of circulating MDSC and the percentage of activated and naïve CD4 T cells were evaluated by flow cytometry. Plasmatic cytokine levels were analyzed by automated ELISA. Results: As previously observed, polymorphonuclear MDSC (PMN-MDSC) frequency was higher in HIV+ patients compared with healthy donors. Furthermore, PMN-MDSC percentage was higher in INR than R patients, and a significant association between MDSC frequency and immunologic failure was confirmed by a receiver operator characteristic analysis. Accordingly, an inverse correlation was found between the percentages of PMN-MDSC and naïve CD4 T cells. A positive correlation was observed between PMN-MDSC frequency and the percentage of human leucocyte antigen locus DR + CD4 T cells and the plasmatic level of IL-1β and IL-8. Conclusion: Our results show that a high frequency of PMN-MDSC persists in INR, possibly because of immune activation, contributing to CD4 T-cell recovery failure. These findings further highlight the detrimental role of MDSC during HIV infection, suggesting these cells as a possible new therapeutic target.

中文翻译：

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简要报告：在接受 cART 治疗的 HIV 感染患者中，免疫失败与高骨髓源性抑制细胞频率相关

背景：在 HIV 感染期间，有效的联合抗逆转录病毒治疗可抑制病毒复制并恢复循环 CD4 的数量+T细胞。然而，15%–30% 的治疗患者对联合抗逆转录病毒治疗的反应不一致。骨髓源性抑制细胞 (MDSC) 在 HIV + 患者中扩增；为了更好地了解 MDSC 对 CD4 T 细胞恢复的作用，我们评估了联合抗逆转录病毒治疗下 HIV+ 患者中 MDSC 的频率及其与免疫反应的关系。 方法：我们招募了 60 名 HIV+ 患者，包括完全缓解者 (R, n = 44)、病毒学无反应者 (VNR, n = 5) 和免疫学无反应者 (INR, n = 11)。通过流式细胞术评估循环 MDSC 的频率以及活化和初始 CD4 T 细胞的百分比。通过自动 ELISA 分析血浆细胞因子水平。 结果：正如之前所观察到的，与健康捐献者相比，HIV + 患者的多形核 MDSC (PMN-MDSC) 频率更高。此外，INR 患者中的 PMN-MDSC 百分比高于 R 患者，并且接受操作者特征分析证实了 MDSC 频率与免疫失败之间的显着相关性。因此，发现 PMN-MDSC 和初始 CD4 T 细胞的百分比之间存在负相关。PMN-MDSC频率与人白细胞抗原位点DR+CD4 T细胞百分比以及血浆IL-1β和IL-8水平呈正相关。 结论：我们的结果表明，INR 中持续存在高频率的 PMN-MDSC，可能是由于免疫激活，导致 CD4 T 细胞恢复失败。这些发现进一步强调了 MDSC 在 HIV 感染过程中的有害作用，表明这些细胞可能成为新的治疗靶点。