Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells

• Published in: Scientific reports 2017-07, Vol.7 (1), p.6313-10, Article 6313
• Main Authors: Cimini, Eleonora, Castilletti, Concetta, Sacchi, Alessandra, Casetti, Rita, Bordoni, Veronica, Romanelli, Antonella, Turchi, Federica, Martini, Federico, Tumino, Nicola, Nicastri, Emanuele, Corpolongo, Angela, Di Caro, Antonino, Kobinger, Gary, Zumla, Alimuddin, Capobianchi, Maria Rosaria, Ippolito, Giuseppe, Agrati, Chiara
• Format: Article
• Language: English
• Subjects: 13/21; 13/31; 631/250/2504; 631/250/255/2514; Adult; CD3 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Cell Differentiation; Dengue fever; Dengue Virus - immunology; Effector cells; Female; Granzyme B; Granzymes - metabolism; Humanities and Social Sciences; Humans; Immune response; Immune response (cell-mediated); Immunity, Cellular; Infections; Interferon; Interferon-gamma - metabolism; Lymphocytes T; Male; Middle Aged; multidisciplinary; Pathogenesis; Science; Science (multidisciplinary); T cell receptors; T-Lymphocyte Subsets - immunology; Vaccine development; Vaccine efficacy; Vaccines; Vector-borne diseases; Young Adult; Zika virus; Zika Virus - immunology; Zika Virus Infection - immunology; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-06536-x

The definition of the immunological response to Zika (ZIKV) infection in humans represents a key issue to identify protective profile useful for vaccine development and for pathogenesis studies. No data are available on the cellular immune response in the acute phase of human ZIKV infection, and its role in the protection and/or pathogenesis needs to be clarified. We studied and compared the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections. A significant activation of T-cells was observed during both ZIKV and DENV infections. ZIKV infection was characterized by a CD4 T cell differentiation toward effector cells and by a lower frequency of IFN-γ producing CD4 T cells. Moreover, a substantial expansion of CD3 + CD4 − CD8 − T-cell subset expressing Vδ2 TCR was specifically observed in ZIKV patients. Vδ2 T cells presented a terminally differentiated profile, expressed granzyme B and maintained their ability to produce IFN-γ. These findings provide new knowledge on the immune response profile during self-limited infection that may help in vaccine efficacy definition, and in identifying possible immuno-pathogenetic mechanisms of severe infection.