While a whole-blood clone is useful, it only provides a general picture of what is going on. Next, the scientists turned to a technique called CITE-seq. This allowed them to find out which cells express genes differently between men and women, and what specific proteins they are making. The best part is that CITE-seq can be used with the same blood sample collected from the patient. “There is only one kind of sample and you just have to measure it,” says Tsang.
A specific type of cell seems to be contributing to the response to the flu vaccine: T cells have efficient memories (which are created after an infection and can “remember” the specific pathogen they are exposed to). encountered) with a receptor named GPR56 expressed on their surface. It turned out that the males who had recovered from Covid had more of these cells than the females who had recovered from Covid and the healthy controls. But why do these cells, which appear to be related to Covid, react to the flu vaccine?
“The classic assumption is that the infection will produce virus-specific cells,” says Tsang. But as he explains, this is not necessarily the case. Other more broadly reactive immune cells may also be activated. Called “bystander cells,” these cells respond very quickly to vaccinations, sending out alarm bells that prompt the immune system to produce antibodies in response.
Indeed, when the scientists examined the GPR56-positive T cells, they found that they had similarities to bystander cells that have been known to be activated during Covid-19 infection. acute. Therefore, they hypothesized, these GPR56-positive cells could function in a similar way to outsider cells, persisting in the body after Covid and initiating immune responses to these pathogens. another invader — in this case the flu vaccine.
To prove this theory, scientists need to see how GPR56-positive T cells respond to something like an infection or vaccination. When they isolated these T cells, cultured them in a petri dish, and stimulated them with small signaling molecules called cytokines produced during infection or vaccination, the scientists found that T cells secrete high amounts of inflammatory proteins found in the body. men who have recovered from Covid-19—providing evidence that this cell type may indeed have triggered an immune response that ultimately produces more influenza antibodies. They found their smoking gun.
Consiglio is curious to see, in the future, what the difference in immune systems between men and women who have recovered from Covid can have when a person is actually infected with the flu or another virus. Looking at gender and previous infections also raises questions about how other factors might influence the immune response. Sabra Klein, a microbiologist at Johns Hopkins University, is interested in seeing how certain factors such as age can also affect the equation and possibly create a sliding scale of immune responses. pandemic. “We often treat these types of variables as binary—you are old or young, you are male or female—and we often don’t do enough to interrogate these intersections,” says Klein.
Ultimately, Tsang and his team hope that these results can help scientists design more effective vaccines or figure out how to predict how a person might respond to an infection. They wanted to find out if those GPR-positive cells could be more efficiently prepared to respond to pathogens. On the other hand, scientists are also curious about how these cells (and others) function during autoimmunity, when the immune system goes into overdrive.
Until then, they will continue to appreciate the complexity of the immune system—especially how it has evolved during a pandemic. “We have always considered the human immune system to be a very diverse natural experiment,” says Tsang. Thanks to the pandemic, the opportunity to learn from this experiment is much greater—meaning we now know more about why our immune systems are so different and how they change over time. time.
