Shane Crotty

Professor

Shane Crotty, Ph.D., and his team study immunity against infectious diseases. They investigate how the immune system remembers infections and vaccines. By remembering infections and vaccines, the body is protected from becoming infected in the future. Vaccines are one of the most cost-effective medical treatments in modern civilization and are responsible for saving millions of lives. Yet, good vaccines are very difficult to design, and very few new vaccines have been made in the past 10 years. A better understanding of immune memory will facilitate the ability to make new vaccines.

Most vaccines work because they generate antibodies. Dr. Crotty recently made a seminal finding in how this process occurs (Science 2009). Dr. Crotty said it has been well established that antibody production is a multi-step process that involves interactions between several cellular players, key among them CD4 “helper” T cells, which are disease-fighting white blood cells that tell other cells to produce antibodies in response to infections. “There were different flavors of these CD4 helper T cells and, for many years, we, in the scientific community, thought that one variety of CD4 helper cells (known as Th2 cells) triggered the antibody process. But about 10 years ago, scientists realized this was incorrect and that there must exist a new variety of CD4 helper T cell that initiated antibody production. It was named Tfh.”

Dr. Crotty’s team set out to understand the inner workings of the Tfh pathway. “We discovered that the BCL6 gene was like an on and off switch, or master regulator, in this process. In a series of experiments, we showed that if you turn on this gene, you get more CD4 T helper cells (the Tfh type) and it’s those cells that are telling the B cells to produce antibodies,” he said. The laboratory is now internationally recognized as a leader in Tfh cell biology, having identified the central role of BCL6 in Tfh cells, and elucidated critical aspects of Tfh cellular and molecular biology in animals and humans.

The field of Tfh cell biology has grown rapidly since the seminal publications in 2009, and work from many labs has shown that Tfh cells are important regulators of autoimmune diseases and allergies, in addition to their critical roles in immunity to viruses and bacteria.

Dr. Crotty has a major focus studying human immune responses to vaccines. His lab is hard at work on candidate HIV vaccines with the CHAVI-ID consortium.