Scientists have identified important distinctions in how innate-like T cells develop in humans compared to mice. During early development, the majority of these T cells in the human thymus are not fully equipped to utilize their immune functions. This finding could lead to advancements in preclinical research and potentially new immunotherapy approaches in the future.
Our immune system consists of two main categories: innate and adaptive. Innate immune cells act as the first line of defense, ready to combat invaders and alert the body. On the other hand, adaptive immune cells are more specialized and take longer to respond, allowing for a more targeted attack against threats. In addition, there exist immune cells that bridge these two categories, such as innate-like T cells. Their unique characteristics make them promising for the development of innovative immunotherapies for conditions like cancer.
However, there is still a lack of understanding regarding how these specific T cells function and develop in humans. Assistant Professor Hannah Meyer from Cold Spring Harbor Laboratory (CSHL) and her collaborator, Professor Laurent Gapin from the University of Colorado Anschutz, embarked on research to explore this issue.
“Examining the immune system’s development is as crucial as studying its role in diseases,” explains Salomé Carcy, a former graduate student at Meyer’s lab who co-led the study. “To gain insights into the functional capabilities of immune cells in disease contexts, we need to understand their origins. One key motivation for our work was to see how much of our knowledge from mouse models applies to human physiology.”
The research team found that innate-like T cells mature in distinct ways between humans and mice, with age being a significant factor. They observed that, in early life, most innate-like T cells in the human thymus are limited in their immune abilities, similar to having one hand tied behind their back. In contrast, in adult bloodstreams, these T cells are fully prepared to activate and defend the body at a moment’s notice, a trend consistent in both species.
Meyer emphasizes that these differences are crucial when considering the development and testing of immunotherapies, especially as many preclinical trials utilize mouse models. “We must account for these variations,” Meyer states. “We also want to examine how these differences evolve over time and whether these T cells have enhanced power at various ages. Can this be leveraged for therapeutic purposes?”
Currently, Meyer and her team are delving deeper into the complex behaviors of immune agents like innate-like T cells. Their research may eventually enable scientists to tap into both the innate and adaptive immune systems to create a novel and stronger form of immunotherapy.
