30-60% of the world's population is chronically infected with a tiny brain-eating parasite called Toxoplasma gondii, and maybe you are too! But why don't we feel sick most of the time? This is because our bodies have evolved a set of complex and adept defense mechanisms, collectively known as the adaptive immune system. This consists of a complicated network of various components including chemical signals such as chemokines, hunter/killer cells known as CD8+ T cells, organs such as the lymph nodes, and much more. Together, these components must coordinate a response on time scales ranging from seconds (chemical signaling) to days (successful recovery from illness) or even longer (control of chronic infection or acquired immunity)!
Underlying all of this is cell motility. Together with Chris Hunter's group in the Department of Pathobiology, we have been studying the statistics of immune cell migration. Borrowing techniques from statistical and computational physics, we obtain novel insights into how the adaptive immune response effectively fights infection.
CD8+ T cells are immune cells with the primary goal of search and destroy. The canonical model for immune cell migration is that these cells (and other immune cells) typically migrate via persistent random walks, and perhaps move directionally in response to specific chemical signals. Suprisingly, however, we found that T cells migration does not conform to simple Brownian walk (or persistent Brownian walk) statistics; rather, they perform generalized Lévy walks, alternating between runs and pauses drawn from two different Lévy distributions. This observation raises many new questions about how T cells search for infectious targets and interact with their environment. Additionally, many believe Lévy distributions to underly evolutionarily optimal search strategies. In this case, it appears that T cells migrate by generalized Lévy walks in order to efficiently find invaders. This raises the question: are the migration strategies of other cells tied to their primary function?
Additionally, chemokines play a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. In order to understand the role of the chemokine CXCL10 during chronic infection by T. gondii, we analyze the migration of CD8+ T cells when this chemokine is suppressed. Interestingly, even though T cell motility slowed, and mice deficient in CXCL10 die due to the inability to fight the infection, the character of the walk statistics did not change. Thus, CXCL10 simply assists T cells by shortening the average time to find rare targets.
The video below, produced by Penn's Office of Communications, summarizes this work.
- T. H. Harris, E. J. Banigan, D. A. Christian, C. Konradt, E. D. Tait Wonjo, K. Norose, E. H. Wilson, B. John, W. Weninger, A. D. Luster, A. J. Liu, and C. A. Hunter, Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells, Nature 486, 545 (June 2012).