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Human antigen presenting cells stimulated with Salmonella delivered influenza antigens induce cytokine production and proliferation of human CD4+ T ce

tetano

Editor, Senior Moderator
J Immunol Methods. 2019 Apr 24. pii: S0022-1759(18)30465-4. doi: 10.1016/j.jim.2019.04.006. [Epub ahead of print]
[h=1]Human antigen presenting cells stimulated with Salmonella delivered influenza antigens induce cytokine production and proliferation of human CD4[SUP]+[/SUP] T cells in vitro.[/h] Kim J[SUP]1[/SUP], Hajam IA[SUP]1[/SUP], Lee JH[SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] This study aimed to investigate whether the human antigen presenting cells (APCs) can process and present Salmonella expressing H7N9 hemagglutinin (Sal-HA), neuraminidase (Sal-NA) or M2 ectodomain (Sal-M2e) to T cells and subsequently activate CD4[SUP]+[/SUP] T cell responses in vitro. In this study, APCs generated from human peripheral blood mononuclear cells (PBMCs) were first treated with mitomycin-C, followed by stimulation with Sal-HA, Sal-M2e, Sal-NA or Salmonella alone for 24 h. Subsequently, stimulated APCs were coincubated with untreated PBMCs (1:10) of the same individual for 24 or 72 h and then analysed for cytokine induction and T cell proliferations by qRT-PCR assay and flow cytometry, respectively. Our results demonstrated that APCs stimulated with Sal-HA, Sal-M2e or Sal-NA induced significantly (p < .05) higher CD3[SUP]+[/SUP]CD4[SUP]+[/SUP] T cell proliferations compared to the APCs treated with Salmonella alone. Our data further revealved that APCs treated with Sal-HA induced significantly (p < .05) higher CD3[SUP]+[/SUP]CD4[SUP]+[/SUP] T cell responses compared to the APCs treated with either Sal-M2e or Sal-NA, which both induced almost comparable levels. The T cell proliferation responses were further measured by lymphocyte proliferation assay and the results showed that Sal-HA and Sal-M2e stimulated APCs induced significantly (p < .05) higher proliferations in T cells compared to the APCs stimulated with either Sal-NA or Salmonella alone. With respect to cytokine inductions, APCs treated with either Sal-HA or Sal-M2e induced significantly (p < .05) higher mRNA transcription levels of proinflammatory (IL-1β, IL-6, IL-12 and IL-23), Th1 (IFN-γ), Th17 (IL-17 and IL-21) and Th2 (IL-10 and TGF-β) cytokines in T cells compared to Sal-NA or Salmonella alone treated APCs. In conclusion, we show that Salmonella system can efficiently deliver vaccine antigens to APCs and is, thus, capable to elicit heterologous antigen-specific adaptive immunity.
Copyright ? 2019. Published by Elsevier B.V.


[h=4]KEYWORDS:[/h] Antigen presenting cells; H7N9 influenza antigens; Salmonella; T cell responses

PMID: 31028753 DOI: 10.1016/j.jim.2019.04.006







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