Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune exhaustion driven by antigen in chronic viral infection

15.05.2009
A main reason why viruses such as HIV or hepatitis C persist despite a vigorous initial immune response is exhaustion. The T cells, or white blood cells, fighting a chronic infection eventually wear out.

Researchers at Emory Vaccine Center have demonstrated that exhaustion is driven by how the immune system detects infecting viruses.

To recognize the presence of a viral infection, T cells must be presented with bits of viral protein in a molecular frame supplied by other cells in the body -- called MHC (major histocompatibility complex) class I molecules.

In mice infected by lymphocytic choriomeningitis virus (LCMV), T cells became more or less exhausted depending on how much properly framed viral protein was available.

Insights from the research could guide efforts to revive the immune system in people with chronic viral infections. The results are published online this week in the Proceedings of the National Academy of Sciences.

Working with Vaccine Center director Rafi Ahmed, PhD, postdoctoral fellow Scott Mueller, PhD, examined the effects of limiting what kind of cells could display the viral antigens.

Ahmed is professor of microbiology and immunology at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar.

By performing bone marrow transplants on genetically engineered mice, Mueller created mice with MHC class I molecules on blood and immune system cells but missing from other cells such as nerve cells and connective tissue. LCMV infects both cells that come from bone marrow and cells that don't. But the roles each type of cell plays in communicating the infection to the immune system is different.

"We were trying to sort out which of several factors contribute to T cell exhaustion, such as viral antigen, inflammation and where the immune system encounters the virus," Mueller says. "What came out of these experiments allowed us to answer a broad question: the role of antigen in driving exhaustion."

When injected with LCMV, the altered mice had more energetic and responsive T cells early during the infection. But later, the altered mice had much higher levels of virus and more exhausted T cells. This contrast demonstrates how the level of antigen present is the motor behind immune exhaustion during the chronic infection.

"Early on, the T cells were healthier because they saw less antigen, and only saw it on cells that came from bone marrow," Mueller says. "But later, the immune system had trouble getting rid of the virus because the T cells couldn't recognize infection in cells that were not able to present the viral antigens."

The research was supported by the National Institutes of Health and the Gates Foundation.

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. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, Emory University Orthopaedics & Spine Hospital, the jointly owned Emory-Adventist Hospital, and EHCA, a limited liability company created with Hospital Corporation of America. EHCA includes two joint venture hospitals, Emory Eastside Medical Center and Emory Johns Creek Hospital. The Woodruff Health Sciences Center has a $2.3 billion budget, 18,000 employees, 2,500 full-time and 1,500 affiliated faculty, 4,300 students and trainees, and a $5.5 billion economic impact on metro Atlanta.

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>