1. Multifunctional T cell response in convalescent patients two years after ZIKV infection
- Author
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Felipe Gomes Naveca, Fernanda S. Oliveira, Helton C. Santiago, Michele Faria Ramos, João Hugo Abdalla Santos, Marcela Helena Gonçalves-Pereira, Olindo Assis Martins-Filho, Valdinete Alves do Nascimento, Camila Pereira Queiroz, Andréa Teixeira-Carvalho, Tertuliano Alves Pereira Neto, Ligia Fernandes Abdalla, and Roberta Oliveira-Prado
- Subjects
0301 basic medicine ,Adult ,CD4-Positive T-Lymphocytes ,Male ,Adolescent ,Viral protein ,viruses ,T cell ,Immunology ,Population ,Biology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Virus ,03 medical and health sciences ,Viral Proteins ,0302 clinical medicine ,Antigen ,medicine ,Immunology and Allergy ,Humans ,education ,education.field_of_study ,Immunity, Cellular ,Zika Virus Infection ,virus diseases ,Convalescence ,Cell Biology ,Zika Virus ,biochemical phenomena, metabolism, and nutrition ,Middle Aged ,Virology ,030104 developmental biology ,medicine.anatomical_structure ,Capsid ,Cytokines ,Tumor necrosis factor alpha ,Female ,CD8 ,030215 immunology - Abstract
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.
- Published
- 2020