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https://www.arca.fiocruz.br/handle/icict/43850
MULTIFUNCTIONAL T CELL RESPONSE IN CONVALESCENT PATIENTS TWO YEARS AFTER ZIKV INFECTION
Author
Pereira Neto, Tertuliano Alves
Pereira, Marcela Helena Gonçalves
Queiroz, Camila Pereira de
Ramos, Michele Faria
Oliveira, Fernanda de Fátima Souza de
Prado, Roberta Oliveira
Nascimento, Valdinete Alves do
Abdalla, Lígia Fernandes
Santos, João Hugo Abdalla
Martins Filho, Olindo Assis
Naveca, Felipe Gomes
Carvalho, Andrea Teixeira de
Santiago, Helton da Costa
Pereira, Marcela Helena Gonçalves
Queiroz, Camila Pereira de
Ramos, Michele Faria
Oliveira, Fernanda de Fátima Souza de
Prado, Roberta Oliveira
Nascimento, Valdinete Alves do
Abdalla, Lígia Fernandes
Santos, João Hugo Abdalla
Martins Filho, Olindo Assis
Naveca, Felipe Gomes
Carvalho, Andrea Teixeira de
Santiago, Helton da Costa
Affilliation
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Análises Clínicas e Toxicologia. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Departamento de Análises Clínicas e Toxicologia. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Leonidas e Maria Deane. Manaus, AM, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil
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 IFN , IL-17A, TNF, and IL-10 production by T cell populations. IFN 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 IFN + TNF+ CD8+ T cell population in response to most virus antigens and CD4+ and CD8+ T cells that were IFN + 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.
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