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Phenotypic and Functional Differences Between HHV-6 and HCMV Specific T-Cells

Solène Fastenackels et.al. , Journal of Virology (2019) - PMID: 30996090

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Abstract

Background: Human herpesvirus 6 (HHV-6) infects over 90% of the population, and establishes a latent infection, with asymptomatic episodes of reactivation. However, HHV-6 reactivation is associated with morbidity and sometimes mortality in immunocompromised patients. To date, the control of the virus in healthy virus carriers and its failure in patients with disease remain poorly understood. In particular, knowledge on HHV-6 specific T-cell responses is limited.Methods: Here, we characterized HHV-6A and 6B specific CD4+ and CD8+ T-cell responses from peripheral blood mononuclear cells (PBMCs) of healthy donors. We studied the phenotype of effector HHV-6 specific T-cells ex vivo, as well as of induced specific suppressive regulatory CD4+ T-cells in vitro post-stimulation, in comparison to human cytomegalovirus (HCMV) responses.Results: Compared to HCMV, we show that ex vivo T-cell reactivity in peripheral blood is detectable but at very low frequency, both for HHV-6A and 6B viruses. Interestingly, the phenotype of the specific T-cells is also different between both viruses. HHV-6A and 6B specific CD4+ T lymphocytes are less differentiated than HCMV specific T-cells. Furthermore, we show a higher frequency of HHV-6 specific suppressive Treg (eTreg) than HCMV specific eTreg in co-infected individuals.Conclusions: Despite the strong similarity of HHV-6 and HCMV from a virologic point of view, we observed immunological differences, in particular related to the frequency and phenotype of effector/memory and regulatory virus specific T-cells. This suggests that different immune actors are solicited in the control of HHV-6 compared to HCMV infection.ImportanceT-cells are central to an effective defense against persistent viral infections that can be related to human cytomegalovirus (HCMV) or human herpes virus 6 (HHV-6). However, knowledge on HHV-6 specific T-cell responses is limited.In order to deepen our knowledge on T-cell responses to HHV-6, we have characterized the HHV-6A and 6B specific CD4+ and CD8+ T-cell responses directly ex vivo from healthy co-infected blood donors.Despite the strong similarity of HHV-6 and HCMV from a virologic point of view, we observed immunological differences, in particular related to the frequency and phenotype of effector/memory and regulatory virus specific T-cells. This suggests that different immune actors are solicited in the control of HHV-6 compared to HCMV infection.Our findings may encourage immunomonitoring of patients with viral replication episodes to follow the emergence of effector vs regulatory T cells.

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