Pharmacology and Regenerative Medicine Dept Visiting Professor Series: Ulrich H von Andrian, MD, PhD

Lecture
Noon-1 p.m., Immune Surveillance by Anti-Viral T Cells

Speaker Bio: Ulrich H von Andrian, MD, PhD,”Uli,” received his medical degree from the Ludwig-Maximilians University in Munich, Germany, where he also conducted doctorate research on blood-brain barrier dysfunction following brain injury. In 1989, he joined the La Jolla Institute for Experimental Medicine and UCSD as a postdoctoral fellow working with Dr. Karl-E. Arfors. His postdoctoral research involved the development of intravital microscopy techniques that led to the discovery of the multistep leukocyte adhesion cascade in vivo. After a second postdoctoral fellowship in the laboratory of Dr. Eugene C. Butcher at Stanford University, Dr. von Andrian joined the Faculty of Harvard Medical School in 1994. He was appointed to his current position in 2006. His scientific research is focused on the regulation and function of immune cells in health and disease. To this end, his laboratory employs intravital microscopy techniques combined with other experimental approaches to study the migration, communication, differentiation and function of immune cells in living animals.

Short Summary: Viral infections trigger vigorous responses by CD8 T cells that differentiate into phenotypically and functionally diverse effector cells (Teff), which give rise to several distinct subsets of long-lived memory cells (Tmem). During the peak anti-viral response, the most frequent T cells in peripheral blood are terminally differentiated CD62L– KLRG1hi CX3CR1hi Teff. We observed that this Teff subset, as well as CX3CR1hi effector memory cells (Tem), cannot access the extravascular space in most tissues, but instead survey microvessels by slowly crawling in the vascular lumen. Unlike crawling myeloid leukocytes, crawling Teff and Tem showed a profound directional bias; free flowing blood-borne cells initially adhered to the vascular wall in venules and then migrated upstream through capillaries into arterioles, which harbored the highest density of crawling cells. Crawling Teff remained continuously motile, even in the face of very high shear stress, but rapidly stopped when endothelial cells displayed a cognate antigen. The adhesion mechanisms of intravascular Teffs crawling and its impact on memory cell formation will be discussed.