Multifunctional T cell response in convalescent patients two years after ZIKV infection

• Published in: Journal of leukocyte biology Vol. 108; no. 4; pp. 1265 - 1277
• Main Authors: Pereira Neto, Tertuliano Alves, Gonçalves‐Pereira, Marcela Helena, Queiroz, Camila Pereira, Ramos, Michele Faria, Oliveira, Fernanda de Fátima Souza, Oliveira‐Prado, Roberta, do Nascimento, Valdinete Alves, Abdalla, Ligia Fernandes, Santos, João Hugo Abdalla, Martins‐Filho, Olindo Assis, Naveca, Felipe Gomes, Teixeira‐Carvalho, Andrea, Santiago, Helton da Costa
• Format: Journal Article
• Language: English
• Published: United States 01.10.2020
• Subjects: Adolescent; Adult; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Convalescence; Cytokines - immunology; Female; Humans; immunity; Immunity, Cellular; Male; Middle Aged; multifunctional T cells; Viral Proteins - immunology; Zika; Zika Virus - immunology; Zika Virus Infection - immunology; Zika Virus Infection - pathology; ZIKV; ZIKV; immunity; multifunctional T cells; Zika
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/JLB.4MA0520-708R

Zika is an important emerging infectious disease in which the role of T cells remains elusive. This study aimed to evaluate the phenotype of multifunctional T cells in individuals 2 yr after exposure to Zika virus (ZIKV). We used a library of 671 synthetic peptides covering the whole polyprotein of ZIKV in pools corresponding to each viral protein (i.e., capsid, membrane precursor or prM, envelope, NS1 [nonstructural protein], NS2A + NS2B, NS3, NS4A + NS4B, and NS5) to stimulate PBMCs from individuals previously exposed to ZIKV. We observed an increased frequency of ZIKV‐specific IFNγ, IL‐17A, TNF, and IL‐10 production by T cell populations. IFNγ and TNF production were especially stimulated by prM, capsid, or NS1 in CD8+ T cells and by capsid or prM in CD4+ T cells. In addition, there was an increase in the frequency of IL‐10+ CD8+ T cells after stimulation with prM, capsid, NS1, NS3, or NS5. Multifunctional properties were observed in ZIKV‐specific T cells responding especially to prM, capsid, NS1 or, to a smaller extent, NS3 antigens. For example, we found a consistent IFNγ + TNF+ CD8+ T cell population in response to most virus antigens and CD4+ and CD8+ T cells that were IFNγ + IL‐17A+ and IL‐17A+IL‐10+, which could also produce TNF, in response to capsid, prM, NS1, or NS3 stimulation. Interestingly, CD8+ T cells were more prone to a multifunctional phenotype than CD4+ T cells, and multifunctional T cells were more efficient at producing cytokines than single‐function cells. This work provides relevant insights into the quality of ZIKV‐specific T cell responses and ZIKV immunity. Graphical ZIKV induces type 1 and type 17 immune responses with multifunctional signatures combining IFNγ, TNF, and IL‐17A production by CD4+ and CD8+ T cells