Kimberly D. Klonowski

The Klonowski Lab studies T cell immunity to respiratory infection across the lifespan.

CD8 T cells are important cells of the immune system that circulate in the body and can rapidly respond and mobilize to eliminate cancerous or infected cells. Importantly, these T cells can generate long-lived memory cells that can be recalled quickly to eliminate these threats when encountered a second time. While antibodies have long been perceived to be the gold standard determinant of vaccine efficacy, it is now well appreciated that elicitation of a T cell response may be equally as effective. Moreover, a T cell response is critical to protection from evolving pathogens, which often mutate surface proteins that are the target of antibodies. This occurs as a consequence of selective pressure by the immune system. In contrast, T cells often recognize evolutionarily conserved peptide sequences that are more resistant to selective pressure. Therefore, understanding how to elicit and maintain T cells specific to a given threat or infection is important, with significant translational potential.

Studies from our laboratory and others have demonstrated that the positioning of T cells in the lung after respiratory infection is equally as important to simply forming memory T cells. However, T cells in the lung parenchyma and lung airways generated after influenza infection, referred to as lung tissue-resident (TRM), are not stably maintained. This is in contrast to those generated in other mucosal sites like the skin and intestine after pathogen exposure.

One major research question being pursued in the laboratory is how lung-specific CD8+ TRM are developmentally regulated by the respiratory environment. Understanding the natural impediments to long-lived respiratory immunity may hold the key to development of a universal influenza vaccine.

The second major research question addresses how T cell immunity is regulated early in life. Using neonatal mice and surgical and genetic models that allow us to probe T cell subsets that emerge before and immediately after birth, we can ascertain the specific contribution of distinct T cell subsets to infection early in life. This knowledge is important for the development and enhancement of vaccines for a particularly vulnerable population.