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T cells can search for and destroy cells infected with SARS-CoV-2 (yellow).
NIAID
By Mitch Leslie
ScienceCOVID-19 reports are supported by the Pulitzer Center.
The immune warriors known as T cells help us fight some viruses, but their importance in fighting SARS-CoV-2, the virus that causes COVID-19, has not been clear. Now two new studies reveal that infected people harbor T cells that attack the virus and can help them recover. Both studies also found that some people who have never been infected with SARS-CoV-2 have these cell defenses, most likely because they were previously infected with other coronaviruses.
“These are encouraging data,” says virologist Angela Rasmussen of Columbia University. Although studies don’t clarify whether people who clear a SARS-CoV-2 infection can avoid the virus in the future, they both identified strong T-cell responses, which “bodes well for the development of long-term protective immunity. term”. Rasmussen says. The findings could also help researchers create better vaccines.
The more than 100 COVID-19 vaccines in development focus primarily on another immune response: antibodies. These proteins are produced by B cells and ideally bind to SARS-CoV-2 and prevent it from entering cells. T cells, by contrast, thwart infections in two different ways. Auxiliary T cells stimulate B cells and other immune defenders to action, while killer T cells attack and destroy infected cells. The severity of the disease may depend on the strength of these T-cell responses.
Using bioinformatics tools, a team led by Shane Crotty and Alessandro Sette, immunologists at the La Jolla Institute of Immunology, predicted which fragments of viral proteins would elicit the most potent T-cell responses. They then exposed the immune cells of 10 patients who had recovered from mild cases of COVID-19 to these viral fragments.
All patients carried helper T cells that recognized the SARS-CoV-2 peak protein, which allows the virus to infiltrate our cells.. They also harbored helper T cells that react to other SARS-CoV-2 proteins. And the team detected virus-specific killer T cells in 70% of the subjects, they report today in Cell. “The immune system sees this virus and creates an effective immune response,” says Sette.
The results are consistent with a study published as a preprint on medRxiv on April 22 by immunologist Andreas Thiel of the Charité University Hospital in Berlin and colleagues. They identified helper protein targeting helper T cells in 15 of 18 hospitalized patients with COVID-19.
The teams also asked whether people who have not been infected with SARS-CoV-2 also produce cells that fight it. Thiel and his colleagues analyzed the blood of 68 uninfected people and found that 34% harbored helper T cells that recognized SARS-CoV-2. The La Jolla team detected this cross-reactivity in about half of the stored blood samples collected between 2015 and 2018, long before the current pandemic began. The researchers believe these cells were likely caused by a past infection with one of the four human coronaviruses that cause colds; The proteins in these viruses resemble those of SARS-CoV-2.
The results suggest that “one reason that a large part of the population can deal with the virus is that we may have a small residual immunity from our exposure to common cold viruses,” says viral immunologist Steven Varga of the University of Iowa. However, none of the studies attempted to establish that people with cross-reactivity do not get as sick with COVID-19.
Prior to these studies, the researchers did not know if T cells played a role in the elimination of SARS-CoV-2, or even if they could cause an overreaction of the dangerous immune system. “These documents are really useful because they begin to define the T cell component of the immune response,” says Rasmussen. But she and other scientists caution that the results do not mean that people who have recovered from COVID-19 are protected from reinfection.
To trigger the production of antibodies, vaccines against the virus need to stimulate helper T cells, Crotty notes. “It is encouraging that we are seeing good T-helper responses against SARS-CoV-2 in COVID-19 cases,” he says. The results have other significant implications for vaccine design, says molecular virologist Rachel Graham of the University of North Carolina, Chapel Hill. Most vaccines in development aim to elicit an immune response against the spike, but both studies found that T cells reacted to various viral proteins, suggesting that vaccines that also stimulate the immune system on these proteins may be more effective. . “It is important not just to focus on one protein,” says Graham.
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