The human immune system contains a rich diversity of cell types, all with unique functions, and many with the ability to adapt to fight different pathogens. Being able to harness and manipulate immune cells is the dream of many disease researchers, as the immune system is a key player in many therapies such as vaccines and cancer treatments. Understanding how immune cells change in response to infection is the first step in being able to boost or dampen this response to improve medical treatments. VIDD Assistant Member Dr. Martin Prlic is studying how two types of immune cells, T cells and natural killer cells, respond to infection. Ultimately, he hopes to apply his findings to improve vaccine development and prevent post-transplant infections.
Following a challenge to the immune system such as exposure to a pathogen or a vaccine, T cells undergo a rapid expansion phase that results in a large population of antigen-specific cells, or cells that are able to respond to the specific foreign invader. After expansion, 90 percent of the cells die off and the remaining 10 percent persist in the body as memory T cells, cells that allow our body to maintain immunity to a given disease for years or decades following infection or vaccination.
Tweaking the contraction phase of this process to increase or decrease the pool of memory T cells could vastly improve current clinical treatments for various diseases, Prlic said. In the case of vaccines or adoptive immunotherapy, the goal would be to increase the specific memory T cells to improve the immune response in fighting off the given disease. In contrast, stem cell or organ transplants rely on dampening the immune system so that the patient’s body doesn’t reject the donation, so specifically decreasing this pool of T cells as opposed to the whole immune system would improve transplant treatments by reducing opportunistic infections.
“If we have a good understanding of how we can manipulate T cell survival or function, we can use that in whatever context we need to,” Prlic said, “whether it’s in an infectious disease or adoptive immunotherapy context to boost T cell numbers, or inducing cell death in the case of a transplant or cancer.”
Prlic’s group found that the protein Bim promotes the programmed cell death, or apoptosis, of T cells during the contraction phase in mice. Now, he wants to know how one can regulate Bim expression to push the balance of memory T cells higher or lower. To do this, his group will use a light-sensitive genetic construct in T cells to specifically modify cell metabolism, which affects Bim levels, to study the protein’s direct effect on these cells.
Prlic is also interested in studying natural killer (NK) cells, immune cells that induce apoptosis of infected human cells. NK cells are among the first to rebound after bone marrow transplants, and are important in staving off opportunistic infections that can occur in this delicate period where the patient’s immune system is repressed. Prlic wants to find ways to boost this cell population to come back faster and stronger in these patients, to further prevent post-transplant complications. He has found that a protein complex containing the immune signaling molecule IL-2 and IL-2 antibodies boosts NK cell numbers in mice, and is now testing whether these cells are active and functional over the long term following a transplant.
Prlic is excited to have many colleagues in VIDD who can assist in figuring out which findings in mice might best translate to the clinic. “This is the perfect place to do these experiments,” he said. “There are great people here who can help judge what can go to clinical trials.”
For more information, see the Prlic lab website