Susan Kaech likes to open research talks with a couple of easy questions for the audience. First "Who here has had the chickenpox?" And then "Who has had it twice?" When almost all of the hands drop, it's a simple display of the effectiveness…
Susan Kaech likes to open research talks with a couple of easy questions for the audience. First "Who here has had the chickenpox?" And then "Who has had it twice?" When almost all of the hands drop, it's a simple display of the effectiveness of "memory T cells"—the type of immune cells she studies. During an infection, these cells are designated to recognize the foreign virus or bacterium responsible to protect against future infections. The desire to study the immune system's memory keepers struck Kaech while in her last year of graduate school at Stanford University. Although working in a developmental biology laboratory at the time, she found herself drawn to some of her friends' research projects in the immunology department. "I was fascinated," she recalls, "by the power and specialization of the immune system, which is constantly exposed to pathogens but fights them off." To help ground herself in the field's basics, she sat in on many of the immunology graduate-level lectures. When one professor discussed memory T cells, Kaech was hooked. Until that moment, she says, "I had never thought about why you become resistant after your first infection or about the cells involved in the process. It really is an amazing phenomenon." Now at Yale University, Kaech and her laboratory colleagues tease apart what makes a T cell turn into a memory T cell. In general, the process starts with "naïve" T cells coming upon a pathogen the immune system has not encountered before and becoming activated by the invader. These T cells then multiply into millions of "effector" T cells, which shut down the infection by either killing or directing the killing of infected cells in the body. Once their job is done, 90–95 percent of the effector T cells die off, but the remainder persist as memory T cells that protect against the same infection later in life. How do these memory T cells form during an infection? An important advance came from Kaech and others in the field when they closely inspected and compared the T cells produced during an infection. This work led to discovery of the small population of T cells that is specifically inclined to become these longest-lived and self-renewing memory cells. Now Kaech is trying to determine what kinds of genetic cues, or switches, guide a T cell along this developmental pathway. Her lab will probe the genome and proteome of T cells as they differentiate from naïve to activated to effector and finally to memory T cells. Understanding how memory T cells form should clarify why the body fails to generate memory T cells effectively in certain cases, such as malaria infections or in response to certain vaccines. If immunologists knew the complete set of signals that lead to the development of a memory T cell, "we might harness that information to make a larger population of them," says Kaech. "This would have a very large impact on improving vaccine design." In addition, researchers might one day be able to tweak the signaling pathway to keep the effector T cells killing infectious agents for a longer time before they themselves die. As such, they might effectively fight off chronic infections or even cancerous tumors. Cancer cells are often recognized by T cells in the same way as infected cells, but the quickly dividing tumor cells frequently outlast or directly suppress the T cell response. While it's clear that the question of cell fate in immunology captured Kaech's imagination for the long term, she says it was "random fate" that led her to science in the first place. As a work-study college student at the University of Washington in Seattle, Kaech chose "lab dishwasher" from a catalog of hundreds of campus jobs. "The postdoc took me under his wing, letting me do some lab work like isolating DNA and culturing cells, and I never looked back."