Loss of T-Cell Multifunctionality and TCR-Vβ Repertoire Against Epstein-Barr Virus Is Associated With Worse Prognosis and Clinical Parameters in HIV+ Patients

• Published in: Frontiers in immunology Vol. 9; p. 2291
• Main Authors: Hernández, Diana M., Valderrama, Sandra, Gualtero, Sandra, Hernández, Catalina, López, Marcos, Herrera, Maria Victoria, Solano, Julio, Fiorentino, Susana, Quijano, Sandra
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.10.2018
• Subjects: EBV; effector T cells; HIV; Immunology; memory T cells; non-Hodgkin B-cell lymphoma; T-cell multifunctionality; HIV; effector T cells; EBV; TCR-Vβ repertoire; memory T cells; non-Hodgkin B-cell lymphoma; T-cell multifunctionality
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02291

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 (EBV HIV ) 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.