Featured Research

from universities, journals, and other organizations

Molecular root of 'exhausted' t cells in chronic viral infection

Date:
November 29, 2012
Source:
Perelman School of Medicine at the University of Pennsylvania
Summary:
In the case of such pathogens as hepatitis C, HIV, and malaria, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the cells become “exhausted” and the immune system can collapse, giving the pathogen the edge. A new study is showing how that happens, suggesting a novel approach that might shift the balance of power in chronic infections.

When you get an acute infection, such as influenza, the body generally responds with a coordinated response of immune-cell proliferation and attack that rapidly clears the pathogen. Then, their mission done, the immune system stands down, leaving a population of sentinel memory cells to rapidly redeploy the immune system in the event of reinfection.

This is why vaccination works, and it's why, in theory at least, people who have had the chicken pox once will never get it again.

But what about chronic infection? In the case of such pathogens as hepatitis C, HIV, and malaria, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the cells become "exhausted" and the immune system can collapse, giving the pathogen the edge.

Now, a new study by researchers at the Perelman School of Medicine, University of Pennsylvania, is showing just how that happens. The findings also suggest a novel therapeutical approach that might be used to shift the balance of power in chronic infections. The study appears in the November 30 issue of Science.

The team, led by E. John Wherry, PhD, associate professor of Microbiology and Director of the Institute for Immunology, used a mouse model of chronic viral infection to map the T-cell response that arises when the immune system is on an extended war footing. They found that two distinct classes of virus-specific CD8+ T cells -- one expressing high levels of the protein T-bet, the other expressing high levels of the protein Eomes, work together to keep the infection in check.

Specifically, they found that the two cell populations appear to have a progenitor-mature cell relationship. The T-bet-expressing cells appear to function as the progenitor cells -- that is, stem cells. These cells divide both to regenerate and maintain the pool of virus-specific T cells. But they also divide and differentiate to form mature, terminally differentiated Eomes-expressing cells. These cells are more effective at fighting the virus itself, but cannot replicate.

"There's a balance, an equilibrium, which allows you to maintain control over the infection but is insufficient to give you complete clearance," Wherry explains.

These two cell subpopulations tend to confine themselves to different anatomic regions in the infected animals, the researchers found. T-bet-positive cells were found in the blood and spleen, whereas Eomes cells were found in the liver, bone marrow, and gut.

Loss of either subpopulation, which the researchers modeled by deleting one or the other protein, reduces the immune system's ability to fight the infection, leading to a shift in favor of the pathogen.

According to Wherry, these data can help explain the gradual loss of virus-specific T cells observed in such chronic infections as hepatitis C.

"Our data suggest the reason for loss of immune control during some chronic infections is that the long-term pressure on this progenitor-mature cell relationship depletes the progenitor pool," he says.

What's more, the study suggests new therapeutic avenues that can be used to fight, or at least better control, chronic infections. For instance, he says, "If we can maintain these progenitor cells longer, or coax the terminal progeny to divide further, we may be able to shift the balance and maintain control of the infection," he says.

Wherry's lab is now studying candidate molecular pathways to determine their efficacy in controlling, and perhaps modulating, these two T-cell populations.

Penn authors include Michael A. Paley, Pamela M. Odorizzi, Jonathan B. Johnnidis, Douglas V. Dolfi, Burton E. Barnett.

The study was funded by National Institutes of Health grants T32-AI-07324; AI0663445; AI061699; AI076458; AI083022, AI078897, HHSN266200500030C; AI082630, and the Dana Foundation.


Story Source:

The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. A. Paley, D. C. Kroy, P. M. Odorizzi, J. B. Johnnidis, D. V. Dolfi, B. E. Barnett, E. K. Bikoff, E. J. Robertson, G. M. Lauer, S. L. Reiner, E. J. Wherry. Progenitor and Terminal Subsets of CD8 T Cells Cooperate to Contain Chronic Viral Infection. Science, 2012; 338 (6111): 1220 DOI: 10.1126/science.1229620

Cite This Page:

Perelman School of Medicine at the University of Pennsylvania. "Molecular root of 'exhausted' t cells in chronic viral infection." ScienceDaily. ScienceDaily, 29 November 2012. <www.sciencedaily.com/releases/2012/11/121129143153.htm>.
Perelman School of Medicine at the University of Pennsylvania. (2012, November 29). Molecular root of 'exhausted' t cells in chronic viral infection. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2012/11/121129143153.htm
Perelman School of Medicine at the University of Pennsylvania. "Molecular root of 'exhausted' t cells in chronic viral infection." ScienceDaily. www.sciencedaily.com/releases/2012/11/121129143153.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins