Grupo de Inmunobiología y Biología Celular, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Grupo de Investigación en Enfermedades Infecciosas, Hospital Universitario San Ignacio, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
Front Immunol. 2018 Oct 4;9:2291. doi: 10.3389/fimmu.2018.02291. eCollection 2018.
Epstein-Barr virus (EBV) is an oncogenic virus associated with the development of aggressive and poor-prognosis B-cell lymphomas in patients infected with human immunodeficiency virus (HIV patients). The most important risk factors for these malignancies include immune dysfunction, chronic immune activation, and loss of T-cell receptor (TCR) repertoire. The combination of all these factors can favor the reactivation of EBV, malignant cell transformation, and clinical progression toward B-cell lymphomas. The overarching aim of this study was to evaluate the frequency, phenotype, functionality, and distribution of TCR clonotypes for EBV-specific T-cell subpopulations in HIV patients at different clinical stages and for HIV patients with B-cell lymphoma, as well as to establish their association with clinical variables of prognostic value. Factors were studied in 56 HIV patients at different clinical stages and in six HIV+ subjects with diagnosed B-cell lymphoma. We found a significant decrease in all subpopulations of EBV-specific CD4 T cells from HIV patients at stage 3 and with B-cell lymphoma. EBV-specific effector CD8 T cells, particularly effector memory cells, were also reduced in HIV patients with B-cell lymphoma. Interestingly, these cells were unable to produce IFN-γ and lacked multifunctionality in HIV+ patients. The TCR-Vβ repertoire, which is key for protection against EBV in healthy individuals, was less diverse in HIV patients due to a lower frequency of TCR-Vβ2, Vβ4, Vβ7.1, Vβ9, Vβ13.6, Vβ14, Vβ17, Vβ22 CD4, Vβ14, and Vβ17 CD8 T cells. HIV patients with positive plasma EBV loads (EBVHIV) had a noteworthy decrease in the levels of both TNF-α and multifunctional TNF-α/IL-2 and TNF-α/IFN-γ CD8 T cells. Altogether, our findings demonstrate that HIV patients have significant alterations in the immune response to EBV (poor-quality immunity) that can favor viral reactivation, escalating the risk for developing EBV-associated B-cell lymphomas.
EB 病毒（EBV）是一种致癌病毒，与感染人类免疫缺陷病毒（HIV 患者）的患者中侵袭性和预后不良的 B 细胞淋巴瘤的发展有关。这些恶性肿瘤的最重要危险因素包括免疫功能障碍、慢性免疫激活和 T 细胞受体（TCR） repertoire 的丧失。所有这些因素的结合可以促进 EBV 的重新激活、恶性细胞转化以及向 B 细胞淋巴瘤的临床进展。本研究的主要目的是评估不同临床阶段的 HIV 患者和 HIV 合并 B 细胞淋巴瘤患者中 EBV 特异性 T 细胞亚群的频率、表型、功能和分布，并确定它们与具有预后价值的临床变量的相关性。研究了 56 名不同临床阶段的 HIV 患者和 6 名诊断为 B 细胞淋巴瘤的 HIV+受试者中的这些因素。我们发现，来自 HIV 患者（处于第 3 阶段和患有 B 细胞淋巴瘤的患者）的所有 EBV 特异性 CD4 T 细胞亚群的数量均显著减少。患有 B 细胞淋巴瘤的 HIV 患者的 EBV 特异性效应 CD8 T 细胞，尤其是效应记忆细胞，也减少了。有趣的是，这些细胞无法产生 IFN-γ，并且在 HIV+患者中缺乏多功能性。在健康个体中，TCR-Vβ repertoire 是针对 EBV 保护的关键，由于 TCR-Vβ2、Vβ4、Vβ7.1、Vβ9、Vβ13.6、Vβ14、Vβ17、Vβ22 CD4、Vβ14 和 Vβ17 CD8 T 细胞的频率较低，因此在 HIV 患者中多样性降低。具有阳性血浆 EBV 载量（EBVHIV）的 HIV 患者的 TNF-α 和多功能 TNF-α/IL-2 和 TNF-α/IFN-γ CD8 T 细胞水平均显著下降。总之，我们的研究结果表明，HIV 患者对 EBV 的免疫反应存在显著改变（免疫质量差），这可能有利于病毒重新激活，增加发展 EBV 相关 B 细胞淋巴瘤的风险。
