Active Infection & Immunity Cancer

Human antigen-specific T cell responses in viral control and immunopathology

In plain English

AI plain-English summary

A single type of immune cell—the cytotoxic T cell—can either clear a virus from the body or, if it responds weakly or inappropriately, make an infection worse. This matters because vaccines and therapies for viruses such as SARS-CoV-2 often focus on antibodies, but T cells are critical for long-term protection and for preventing damage in infected organs. The researchers have already built platforms to isolate T cells from blood and tissue, measure their function, and link that to genetic and receptor data. Now they want to answer fundamental questions about how T cells form memory—especially tissue-resident memory cells that stay in the lungs or other organs—and how that memory is maintained after infection or vaccination. If this work succeeds, it could provide the scientific basis for designing vaccines that deliberately induce the right kind of T cell response, and for therapies that prevent T cells from causing harmful inflammation. This is primarily fundamental science: it aims to understand a core mechanism of immune memory. Similar fundamental work on T cell biology has previously underpinned breakthroughs in cancer immunotherapy and vaccine development.

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The main objective of my group is to investigate the functional aspects of antigen specific cytotoxic T cells (CTL) with a focus on the factors affecting CTL in controlling virus infection and cancer progression.While a robust and appropriate T cell response is typically beneficial to the host during human infections, a weak or inappropriate response can be ineffective or even have a detrimental effect. Over the past two decades, our efforts have been on understanding the key factors required for efficient viral control by T cells in a number of different viral infections and cancer. To do this, we have established an ex-vivo and in-vitro T cell functional evaluation platforms for antigen-specific T cells isolated from tissue and blood. By linking these functional data with multi-omic single cell and T cell receptor (TCR) repertoire analysis, we have identified potential targets and pathways to augment and control the immune response as a way of improving the outcome of several important human diseases including SARS-CoV-2 virus infection. In this proposal, we will address fundamental questions in CTL memory induction, central memory establishment and maintenance following virus infection and vaccination, with a particular focus on tissue-resident memory cells using SARS-CoV-2 as the model system. We aim to establish CTL functional relevance to efficient viral control and potential detrimental immunopathology in affected organs. By studying the immunology of tissues, we will provide scientific evidence and tools for improved vaccine design and therapeutic approaches for virus infections.

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Researchers

Tao Dong (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Investigating how memory T cells regulate immune responses to re-infection and cancer
The T cell immune response to cytomegalovirus across the adult lifecourse
A novel pathway in the control of memory T cell function during immune responses to viral re-infection.
Defining high-resolution T-cell correlates of protection in abortive versus seropositive SARS-CoV-2 infection
Dynamic changes at the immune synapse controlling CTL function

Original classification

Research Grant

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