Whole-blood transcriptomics were helpful, but they only provided a complete picture of what was going on. Next, the scientists turned to his technique called CITE-seq. This allowed us to see which cells expressed which genes differently in males and females, and what specific proteins they were making. The best part was being able to use her CITE-seq on the same blood sample taken from the patient. “He only has one sample, and he just measures it,” he says.
A specific type of cell appeared to contribute to the response to the influenza vaccine: efficacious memory T cells (generated after infection and capable of identifying specific pathogens encountered) that express a receptor called GPR56 on their surface. After all, Covid-recovered men had more of these cells compared to Covid-recovered women and healthy controls. Why are these cells that look like they respond to the flu vaccine?
“The standard assumption is that the infection produces virus-specific cells,” says Tsang. But as he explains, this isn’t always the case. Other, more broadly reactive immune cells can also be activated. These cells, known as “bystander cells,” respond very quickly to vaccination and set off alarm bells for the immune system to respond and make antibodies.
In fact, when scientists examined GPR56-positive T cells, they found that they shared similarities with bystander cells already known to be activated during acute Covid infection. hypothesized that these GPR56-positive cells probably act in a similar way to bystander cells, persisting in the body post-Covid and initiating immune responses against other invaders (in this case, influenza vaccines). rice field.
To prove this theory, scientists needed to see how GPR56-positive T cells respond to something akin to infection or vaccination. When these T cells were isolated, cultured in Petri dishes, and stimulated with small signaling molecules called cytokines known to be produced during infection and vaccination, T cells showed high levels of inflammatory activity. found to secrete proteins. This provides evidence that this cell type may indeed have triggered an immune response and ultimately produced more influenza antibodies. They found a smoking gun.
In the future, Consiglio would like to know how these immune system differences between men and women who have recovered from Covid affect when people actually get the flu or another virus. increase. Looking at gender and previous infections also raises the question of how other factors influence the immune response. I am interested in how it affects and possibly creates a sliding scale of immune response. or female, etc. It’s often not enough to explore these intersections,” says Klein.
Ultimately, Tsang and his team hope that these results will help scientists design more effective vaccines or find ways to predict how people will respond to infection. They want to see if these GPR-positive cells can be more efficiently primed to respond to pathogens. Conversely, scientists are also interested in how these cells (and others) function during autoimmunity, when the immune system is overactive.
Until then, we will continue to understand the intricacies of the immune system, especially how it evolved during the pandemic. “We always thought about looking at the human immune system as a very diverse natural experiment,” says Tsang. Thanks to the pandemic, we have much more opportunity to learn from this experiment. That means we now know more about why our immune systems are so different and how they change over time.
