News Release: Research , School of Medicine

Feb. 17,  2010

Immune Activation Gives T Cells Temporary Pass to the "Front Lines"

News Article ImageRafi Ahmed, PhD, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.

Memory T cells, cells important for strong responses to infections, usually behave as if there's a barrier between the intestines and the rest of the body. However, for a limited time after an infection begins, recently activated T cells can cross the barrier, scientists from Emory Vaccine Center and University of Minnesota Medical School have discovered.

Their findings, published online this week in the Journal of Experimental Medicine, have implications for designing vaccines against challenging infections such as HIV.

Memory T cells - the variety known as CD8+ or "killer" cells -- can eliminate virus-infected cells before the virus can replicate. For a vaccine to be effective, immunologists have thought that it has to get enough memory T cells to "the front lines" in preparation for the invaders' arrival, says first author David Masopust, PhD.

Viruses often get into our bodies by breaching mucosal surfaces such as the soft tissues in the nose, mouth or intestines. Yet most vaccines in use today are given by injection.

"Our results suggest that vaccines may not have to be delivered to oral or mucosal surfaces to establish memory there, but you have to measure local responses at those sites to gauge vaccine effectiveness," he says.

Masopust began his research on memory T cells in Rafi Ahmed's laboratory at Emory, and is now assistant professor of microbiology at University of Minnesota Medical School. Ahmed, director of the Emory Vaccine Center, is a Georgia Research Alliance Eminent Scholar and a member of the National Academy of Sciences.

Masopust and his colleagues investigated a wide array of immune responses, mainly using mice genetically engineered to have many T cells that recognize LCMV (lymphocytic choriomeningitis virus). These T cells were transplanted into a different strain of mice in order to follow their movements around the body during an infection by LCMV, which was begun by injection of the virus into the body cavity.

Before infection, T cells that recognize LCMV circulated in the blood and lymph nodes but not in the small intestine, the authors found.

"These are so-called ‘naïve' cells, before they've seen the virus and before they become memory cells," Masopust says.

After an infection begins, freshly energized T cells recognizing LCMV could move between the intestine and the rest of the body, but the ability to move to the intestine was lost after a week. The cells' physical presence in the intestines matched the appearance of a molecule called integrin ?4?7 on their surfaces: on for a week, then off.

"We can think of this molecule as a temporary pass that allows cells to move around in the intestine," Masopust says. "And it looks like the cells don't have to be activated in the intestines to be able to go there."

Memory T cells from mice that were already immunized with LCMV behaved the same way. Upon infection and activation by the virus, they turned on integrin ?4?7 and moved to the intestine. However, memory T cells didn't keep integrin ?4?7 turned on, and if they were in the intestine, stayed in place and didn't go anywhere else. Even when an intestinal transplant is performed, memory T cells from the recipient don't migrate to the donor stretch of intestine, the authors found.

Memory T cells behaved the same way when responding to a variety of infection routes. For example, when flu virus was administered to mice through the nose, the T cells that responded to flu virus in the lung temporarily had the integrin molecules that allowed them to travel to the intestines. Similar results came when the authors looked at T cells that appeared in response to an intramuscular vaccine or oral infection with Listeria monocytogenes, a bacterium.

Masopust and his colleagues also looked at humans vaccinated against yellow fever. Volunteers gave blood and their T cells were examined for both integrin ?4?7 and the molecule CLA (cutaneous lymphocyte-associated antigen), which allows T cells to stay close to the surface of the skin. Both molecules appeared on the same cells transiently for about a week after immunization.

"These results suggest that T cells' ‘homing' ability is similarly dynamic following a relevant real world vaccination," Masopust says. "The tasks ahead include defining the type of vaccine - live replicating or not -- that best establishes immunity in the intestines. It will be important to examine other mucosal surfaces involved in specific viral infections. For HIV, this means vaginal and rectal surfaces."

The research was supported by the National Institutes of Health and the Arnold and Mabel Beckman Foundation.

Reference:
D. Masopust et al. Dynamic T cell migration program provides resident memory within intestinal epithelium. J. Exp. Med. Page numbers (2010) 10.1084/jem.20090858

###

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.

Learn more about Emory’s health sciences:
Blog: http://emoryhealthblog.com
Twitter: @emoryhealthsci
Web: http://emoryhealthsciences.org

News Release Tools

  • Print

News Releases

The news release you are currently viewing is part of an archive of Emory health sciences press releases, dating Sept. 2008 - Dec. 2011.



To View Current Releases


Emory News Center

Emory News Center



To View News Archives


News Archives

News Archives