Investigation of the generation and functional maturation of regulatory T cells in vivo

  • Funded by UK Research and Innovation (UKRI)
  • Total publications:9 publications

Grant number: MR/S000208/1

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2019
    2022
  • Known Financial Commitments (USD)

    $100,802.96
  • Funder

    UK Research and Innovation (UKRI)
  • Principle Investigator

    Pending
  • Research Location

    United Kingdom, Europe
  • Lead Research Institution

    Imperial College London
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Immunity

  • Special Interest Tags

    Gender

  • Study Subject

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

This important study will explore T-cell immunity to COVID-19. T-cell immunity is considered to play key roles in the eradication of infection by promoting B-cell maturation and eliciting cytotoxic activities to the virus. It is also known that severe COVID-19 patients show remarkable T-cell dysregulation. However, it is unknown known how T-cells respond to each of the key COVID-19 viral antigens, and there is still an urgent need for basic research on the antiviral T-cell immunity using animal models. Accordingly, I propose to investigate T-cell responses to the key COVID viral antigens (including Spike protein) using our mouse models. Specifically we will test if each of the viral proteins induces a particular type of T-cell responses (e.g. Th1 response, Treg induction). We will analyse not only regulatory T-cell (Treg) responses but also helper T-cell responses and CD8+ T-cell responses to the antigen. We will produce recombinant proteins and perform DNA vaccination to analyse T-cell responses. Nr4a3-Tocky and Foxp3-Tocky, which allow the analysis of antigen-reactive T-cells and Treg dynamics, respectively. The level of urgency and importance The proposed project will produce basic materials and knowledge for (1) improving vaccine strategies by enhancing T-cell immunity; (2) improving the COVID-19 immunity test. The fund by converting the two original activities into the COVID-19 research will be equivalent to a 6-month project. We will apply for a follow-on fund through the UKRI and/or industrial grants, in order to further investigate anti-COVID-19 T-cell immunity and develop new methods for fighting COVID-19. The necessary critical mass: The proposed project will be still within the scope of the original plans, i.e. to investigate the mechanism of the generation and functional maturation of Treg in vivo. Instead of using other antigen models, we will use the viral antigens. Thus, we have all the resources including the key transgenic mouse tools (Foxp3-Tocky and Nr4a3-Tocky mice) for the investigation. We will use a commercial maintenance service and their technical supports for maintaining and obtaining the Tocky mice for experiments, in order to smoothly conduct the planned experiments. Strengths: The proposed project will provide key preliminary data for further developing new methods to improve COVID-19 vaccines and immunity tests.

Publicationslinked via Europe PMC

Last Updated:39 minutes ago

View all publications at Europe PMC

Single-Cell Transcriptome Analysis of Treg.

HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia/lymphoma.

NF-κB activation in cardiac fibroblasts results in the recruitment of inflammatory Ly6Chi monocytes in pressure-overloaded hearts.

Application of dual Nr4a1-GFP Nr4a3-Tocky reporter mice to study T cell receptor signaling by flow cytometry.

Restoring control over autoimmunity by inducing Foxp3.

T-cell dysregulation in COVID-19.

T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis.

Corrigendum.