- Our immune systems are complex, with many cells stepping in to fight viruses
- In the case of SARS-CoV-2, researchers wanted to investigate the response of our T cells
- T cell response may explain why some people suffer mild illness and others are hospitalised
Almost a year after the appearance of SARS-CoV-2, the virus that causes Covid-19, we now understand a lot more about the pathogen.
As scientists are trying to find effective vaccines and treatments, many of us are still baffled by the levels of severity of Covid-19 – ranging from asymptomatic to mild to fatal. To try to understand these varying reactions, scientists investigated how exactly the many types of immune cells in our bodies respond to SARS-CoV-2.
Now, a new international study by scientists at the La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton is the first to explain exactly how the CD4+ T cells in our bodies respond to the novel coronavirus. The paper was recently published in the journal Cell.
Do T cells kill off protection?
According to the researchers, there is an urgent need for further investigation into the way our immune systems respond to SARS-CoV-2.
To understand more about the exact mechanisms that affect the severity of Covid-19, the researchers unraveled the way the CD4+ T cells respond to SARS-CoV-2.
These cells play an important role in our adaptive immune systems and help any other immune cells by releasing cytokines in the body.
But the researchers found that patients hospitalised with severe Covid-19 tend to develop a novel T cell subset that can kill B cells, causing the body to develop fewer antibodies.
Until now, studies on CD4+ T cells used limited sets of markers that don’t provide complete insight into the way these cells respond to the coronavirus. In order to more thoroughly investigate CD4+ T cells, the researchers used a technique called single-cell RNA sequencing (RNA seq) to provide a detailed analysis.
Each T cell has a specific role
"CD4+ T cells play a central role in orchestrating the immune response," said study co-first author Benjamin Meckiff, PhD, postdoctoral fellow at LJI. "They are a heterogeneous population of immune cells carrying out a wide range of functions, and we have been able to specifically analyse their response to SARS-CoV-2."
The researchers looked at samples from 40 Covid-19 patients, divided into hospitalised and non-hospitalised groups. They then used the RNA seq technique to see which types of CD4+ T cells responded to the coronavirus in each of these patients.
While these cells all provide protection against pathogens, each T cell has a specific role – the CD4+ cells help alert the body that there’s an intruder by releasing cytokines, while B cells are responsible for making antibodies.
But patients with more severe Covid-19 had T cells that produced too many cytotoxic TFH cells, potentially increasing infection and killing off antibodies from the B cells.
"The TFH cells in hospitalised patients displayed gene signatures that suggest they are dysfunctional and aren't giving the help to B cells that we would expect," says Meckiff.
Important starting point for future investigation
According to the authors, their work has established a baseline for comparing responses in people over time or people with different levels of disease severity.
"Going forward, we can extend this understanding of what's going on in the blood in response to new viruses to understanding what goes on in the tissue when our immune system deals with cancer," said study collaborator Professor Christian Ottensmeier from the University of Liverpool.
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