T-cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection.,Immunology

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T-cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection.
Immunology ( IF 4.9 ) Pub Date : 2020-04-06 , DOI: 10.1111/imm.13185
Marcela Helena Gonçalves Pereira ₁ , Maria Marta Figueiredo ₂ , Camila Pereira Queiroz ₁ , Télcia Vasconcelos Barros Magalhães ₃ , Adriana Mafra ₄ , Lilian Martins Oliveira Diniz ₅ , Último Libânio da Costa ₆ , Kenneth J Gollob ₇ , Lis Ribeiro do Valle Antonelli ₂ , Helton da Costa Santiago _{1,

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Affiliation

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.

中文翻译：

产生IFNγ，TNF和IL10多种组合的T细胞与轻度登革热感染有关。

多功能白介素10（IL10）+ Th1细胞已牵涉许多传染性疾病的有利发展，促进有效的免疫反应，同时限制免疫病理学。在这里，我们调查了在登革热感染期间表达干扰素γ（IFNγ），IL10和肿瘤坏死因子（TNF）或其组合的多功能CD4 +和CD8 + T细胞的存在。在危重病情（严重时（住院期间）和恢复阶段。通过流式细胞术评估CD4 +和CD8 + T细胞产生的IFNγ，IL10和TNF。我们的数据显示，轻度登革热患者与具有警告标志和严重登革热的登革热患者相比，在危急期以及NS3-和N3阶段，出现更高频率的多功能T细胞，如产生NS3特异性IFNγ/ IL10的CD4 + T细胞。 ENV特异性CD8 + T细胞产生IFNγ/ IL10。此外，在轻度登革热组中还观察到产生高水平IFNγ/ TNF和IFNγ/ TNF / IL10的NS3特异性CD8 + T细胞。我们观察到，与单个生产者T细胞相比，按细胞内含量衡量，多功能T细胞产生更高水平的细胞因子。重要的是，产生IFNγ，TNF和IL10的多功能CD4 +和CD8 + T细胞同时显示与血小板水平呈正相关，表明该人群具有保护作用。

更新日期：2020-04-22

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