The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has awarded a $2 million, five-year grant to Ken Oestreich, an assistant professor at the Virginia Tech Carilion Research Institute, to study immunological memory.
The human immune system can "remember" invading pathogens, such as viruses, and can recognize intruders from previous infections and respond more quickly and robustly.
"We want to know how memory cells form as part of the immune response," said Oestreich, who also serves as an assistant professor in both the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine and the Department of Internal Medicine at the Virginia Tech Carilion School of Medicine. "Understanding the ways in which these cells form is critical for the design of more effective vaccines, as well as new therapies that capitalize on the body's natural defense system."
In response to infection by intracellular pathogens, such as influenza, the immune system triggers a boost in the number of specialized immune cells available to fight infection. Called effector T cells, these soldiers differentiate into two classes to battle influenza: T helper 1 (Th1) and T follicular helper (Tfh) cells.
These two effector cell types perform distinct duties as part of an immune response. Th1 cells help coordinate the responses of other immune cells at the site of infection, while Tfh cells help other cells make antibodies specifically designed to eliminate the pathogen. Oestreich and his team previously discovered that, despite their different functions, these T cell populations may be developmentally linked.
As the immune system eliminates the infection, the large population of defending cells is no longer needed, and their numbers wane. However, a small number of cells are left behind. These cells transition from actively fighting to a passive state.
"These new memory T cells are waiting, poised to react should a challenge arise again," Oestreich said.
This means that if the body sees the same pathogen during a future infection, the memory effector T cells bounce back into action, wiping out the disease so efficiently that the host often doesn't even develop symptoms.
It's unclear, though, whether memory cells arise directly from the fighting effector T cells, or whether they form as a separate set of cells during infection. It was previously thought that they use the same battle plan as before, where memory Th1 cells fight at the site of infection, while memory Tfh cells work with other cells to produce antibodies needed to defeat the invader.
"We're questioning that now," Oestreich said. "We have good preliminary evidence suggesting that Th1 cells can give rise to Tfh cells, and that they may transform into memory T cell populations."
That's an important distinction, Oestreich said — it would mean that these cell types aren't as dissimilar as previously thought.
"We're investigating whether Th1 cells can give rise to memory cells," Oestreich said. "This would mean that memory populations can come directly from effector cells, allowing them to switch roles as needed during the course of an immune response."
Ultimately, this means that the immune system may not fight with separately-trained soldiers, but, rather, the soldiers change roles as the environment changes.
"This allows the cells to respond and perform different functions as soon as they are needed," Oestreich said.
The research grant from the NIH allows Oestreich to study exactly how the molecular environment affects effector and memory T cell status and function. Oestreich and his team will use both cells cultured in his laboratory and infection models, such as influenza. By understanding the regulatory pathways of memory cell transitions, scientists may be able to develop increasingly effective vaccines as well as innovate novel immunotherapeutic strategies, according to Oestreich.
Oestreich's research team includes Kaitlin Read, a research specialist and laboratory coordinator, as well as Michael Powell and Bharath Sreekumar, both of whom are doctoral students in Virginia Tech's Translational Biology, Medicine, and Health graduate program.
Other contributors include Coy Allen, an assistant professor in the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine who studies inflammatory diseases; David Xie, an associate professor at the Biocomplexity Institute of Virginia Tech and in the Department of Biomedical Sciences and Pathobiology in the College of Veterinary Medicine, where he studies epigenomics and computational biology; and Andre Ballesteros-Tato, an assistant professor of medicine at the University of Alabama at Birmingham School of Medicine.