Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Longterm immune memory cells cells do not develop during chronic viral infections

08.11.2004


Finding by Emory University scientists has implications for vaccines, antiviral therapies and cancer treatment



Immune T cells that respond to chronic viral infections do not acquire the same "memory" capabilities of T cells that respond to acute viral infections, according to research by scientists at Emory University. The finding may explain why people lose their immunity to some viruses after chronic infections are controlled. It could guide scientists in developing better therapeutic combinations of antiviral therapies and therapeutic vaccines. The research is published online in the Proceedings of the National Academy of Sciences.

Lead author of the study is E. John Wherry, PhD, postdoctoral fellow in the Department of Microbiology and Immunology at Emory University School of Medicine and the Emory Vaccine Center. Senior author is Rafi Ahmed, PhD, director of the Emory Vaccine Center, Georgia Research Alliance Eminent Scholar, and professor of microbiology and immunology.


The immune system responds to viral infections in two ways: with antibodies that help prevent viruses from entering cells and with T cells activated in response to viral antigens. T cells kill the virus-infected cells and produce proteins called cytokines that prevent the growth of viruses and make cells resistant to viral infection. During the acute phase of a viral infection, activated CD8 T cells respond aggressively for a few weeks, then about five percent of them become "memory cells" that maintain a stable memory T cell population by slow, steady turnover. These memory cells are poised to mount an even stronger and more rapid response to future attacks by the same virus. Individuals who acquire immunity to diseases such as measles, yellow fever, smallpox, or polio, either through exposure or vaccination, often are capable of retaining that immunity for many years or for an entire lifetime.

Dr. Ahmed and his colleagues discovered in previous research that following acute viral infections, immune memory CD8 T cells continue to maintain their ability to attack viruses even when they are not continuously stimulated by viral antigen (Science, Nov. 12, 1999). Other studies have suggested, however, that during some chronic infections continuing exposure to viral antigen may be necessary to maintain protective immunity.

The Emory researchers used a mouse model of infection with lymphocytic choriomeningitis virus (LCMV) to study the differences in CD8 memory T cell immune response following acute and chronic infections. In mice with the acute infection, the virus was cleared by a CD8 T cell immune response within one week. In mice with the chronic infection, high virus levels were present in multiple tissues for the first two to three months, then the virus was controlled in most tissues by a T cell response but was not completely eliminated.

To directly compare the memory capabilities of cells from both types of infection, the scientists transferred both acute memory and chronic memory CD8 T cells into uninfected mice, without transferring any of the viral antigen. The acute memory cells were maintained through homeostasis and divided several times, but the chronic memory cells failed to divide and declined in number over time. When the chronic memory CD8 T cells were transferred back into chronically infected mice where they re-encountered antigen, the cells began to recover.

The scientists also compared other important qualities of memory T cells, including the responsiveness to cytokine signaling by interleukin 7 (IL-7) and interleukin 15 (IL-15). Response to these cytokines is a critical part of the immune pathway that allows memory CD8 T cells to undergo homeostatic division and to persist even in the absence of viral antigen. They found that chronic memory CD8 T cells responded poorly to both IL-7 and IL-15, whereas acute memory CD8T cells proliferated in response to both cytokines. Additional research could show whether the defect in chronic memory cell response to IL-7 and IL-15 can be overcome by increasing the expression of these cytokines, or whether other deficiencies in the pathway exist.

"The normal memory CD8 T cell differentiation program that occurs after acute infection results in memory cells that are capable of long-term persistence in the absence of antigen as a result of slow homeostatic proliferation in response to IL-7 and IL-15," said Dr. Ahmed. "We have shown that during chronic LCMV infection this memory pathway does not proceed efficiently and that virus-specific CD8 T cells do not acquire the cardinal property of antigen-independent persistence."

The Emory scientists also concluded that rest from antigen exposure is an important criterion for developing long-term immune memory. Acute memory T cells are exposed to antigen for a finite time period after an acute infection, then after the virus with antigen is eliminated, these cells differentiate into memory T cells. A recent study of HIV infection showed that if antiretroviral therapy is initiated during the early phase of infection, HIV-specific CD8 T cells are maintained more efficiently.

"Our research shows that prolonged exposure to antigen without any rest results in cells that are "addicted" to antigen and cannot persist without it," Dr. Ahmed explains. "This raises concerns about vaccine strategies that use persisting antigen, because antigen-independent memory T cells may not develop."

The study may help explain the loss of T cell immunity seen in some chronic infections that are eventually controlled and eliminated, and the ability of some persistent tumors to provide protection from a secondary tumor challenge if the original tumor is not removed. "Giving T cells a rest by terminating exposure to viral antigen simulation following the acute phase of infection seems to be necessary if T cells are to differentiate into long-term antigen-independent memory T cells," Dr. Ahmed says. "Therapeutic vaccine approaches that provide antigen re-stimulation during persistent infections may not allow the ability for memory T-cell proliferation. However, antiviral therapy or cancer chemotherapy may provide rest from antigen stimulation and allow partial recovery of some memory T cell functions. By combining drug treatment with therapeutic vaccination or cytokine therapies we may be able to prevent loss of T cell memory and establish long-term protective immunity."

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

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>