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T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection
Author(s) -
Gonçalves Pereira Marcela Helena,
Figueiredo Maria Marta,
Queiroz Camila Pereira,
Magalhães Télcia Vasconcelos Barros,
Mafra Adriana,
Diniz Lilian Martins Oliveira,
Costa Último Libânio,
Gollob Kenneth J.,
Antonelli Lis Ribeiro do Valle,
Santiago Helton da Costa
Publication year - 2020
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13185
Subject(s) - dengue fever , interleukin 10 , cd8 , immunology , interferon gamma , immune system , tumor necrosis factor alpha , biology , interferon
Summary Multifunctional interleukin 10 (IL10) + Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4 + and CD8 + T‐cells that expressed interferon gamma (IFNγ), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNγ, IL10 and TNF by CD4 + and CD8 + T‐cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T‐cells like NS3‐specific IFNγ/IL10‐producing CD4 + T‐cells in critical phase and NS3‐ and ENV‐specific CD8 + T‐cells producing IFNγ/IL10. In addition, NS3‐specific CD8 + T‐cells producing high levels of IFNγ/TNF and IFNγ/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T‐cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T‐cells. Importantly, multifunctional CD4 + and CD8 + T‐cells producing IFNγ, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10 + Th1 and IL10 + Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.