Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy.
Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy.
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DOI：
10.3389/fimmu.2022.869286
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
尽管抗逆转录病毒疗法(ART)的广泛应用在控制HIV复制和促进CD4+T细胞恢复方面取得了很大进展，但一些患者的免疫重建仍然不足，他们被定义为免疫应答差(PIRS)。这些PIR是艾滋病相关并发症和非艾滋病并发症的高危人群，导致较高的发病率和死亡率。因此，早期识别PIRS并及时提高其免疫功能是一项重大挑战和迫切需要。免疫激活是导致接受有效抗逆转录病毒治疗的艾滋病毒携带者(PLWH)免疫重建受损的关键因素。双阴性T细胞(DNT)被报道与HIV感染过程中的免疫激活控制有关。然而，DNT细胞在HIV感染过程中发挥抑制能力的确切机制仍然令人困惑。CD73既是可溶性的，也是膜结合型的，通过产生腺苷(ADO)发挥免疫抑制作用。因此，DNT细胞是否表达CD73并通过CD73-ADO途径介导免疫抑制尚需进一步研究。在这里，我们发现与健康对照组相比，初治PLWH(TNS)患者DNT细胞上CD73表达显著下调，同时血浆中sCD73浓度增加。经ART治疗后，CD73+DNT细胞比例和血浆sCD73水平均恢复正常。然而，与免疫反应者(IRS)相比，PIRS显示CD73+DNT细胞的百分比降低。PLWH患者CD73+DNT细胞百分率与CD4+T细胞计数、CD4/CD8比值呈正相关，与免疫激活呈负相关。SCD73水平与CD_4~+T细胞计数、CD_4/CD_8比值呈负相关。更重要的是，在目前的队列中，启动ART时sCD73水平较高可以预测长期ART后PLWH免疫重建不良。我们的发现强调了CD73+DNT细胞和sCD73在PLWH的疾病进展和免疫重建中的重要性，并为sCD73作为预测免疫恢复的潜在生物标志物提供了证据。
Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.
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影响因子：
7.3
作者：
Bandera A;Masetti M;Fabbiani M;Biasin M;Muscatello A;Squillace N;Clerici M;Gori A;Trabattoni D
通讯作者：
Trabattoni D
影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
影响因子：
4.2
作者：
Hixson EA;Borker PV;Jackson EK;Macatangay BJ
通讯作者：
Macatangay BJ
影响因子：
19
作者：
Alcedo KP;Bowser JL;Snider NT
通讯作者：
Snider NT
影响因子：
4.4
作者：
Clayton, Aled;Al-Taei, Saly;Tabi, Zsuzsanna
通讯作者：
Tabi, Zsuzsanna