Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

'Pep talk' can revive immune cells exhausted by chronic viral infection

14.12.2011
Chronic infections by viruses such as HIV or hepatitis C eventually take hold because they wear the immune system out, a phenomenon immunologists describe as exhaustion.

Yet exhausted immune cells can be revived after the introduction of fresh cells that act like coaches giving a pep talk, researchers at Emory Vaccine Center have found. Their findings provide support for an emerging strategy for treating chronic infections: infusing immune cells back into patients after a period of conditioning.

The results are published this week in Proceedings of the National Academy of Sciences Early Edition.

The first author of the paper is Rachael Aubert, a student in Emory's Immunology and Molecular Pathogenesis program who completed her doctorate in 2009. Senior author Rafi Ahmed, PhD, is director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.

Ahmed's laboratory has extensive experience studying mice infected with lymphocytic choriomeningitis virus (LCMV). Immune responses against LCMV are driven by CD8 or "killer" T cells, which destroy virus-infected cells in the body. But a few weeks after exposure to LCMV, the mice develop a chronic infection that their immune systems cannot shake off, similar to when humans are infected by viruses like HIV and hepatitis C.

Aubert and her co-workers examined what happened to mice chronically infected with LCMV when they infused CD4 or "helper" T cells from uninfected mice. After the infusion, the CD8 cells in the infected mice revived and the levels of virus in their bodies decreased by a factor of four after a month. Like coaches encouraging a tired athlete, the helper cells drove the killer cells that were already in the infected mice to emerge from exhaustion and re-engage.

The cell-based treatment was especially effective when combined with an antibody that blocks the molecule PD-1, which appears on exhausted T cells and inhibits their functioning. The antibody against PD-1 helps the exhausted T cells to revive, and enhances the function of the helper cells as well: the combination reduced viral levels by roughly ten-fold, and made the virus undetectable in some mice.

"We have not seen this sharp of a reduction in viral levels in this system before," says co-author Alice Kamphorst, a postdoctoral fellow.

The helper cells were all genetically engineered to recognize LCMV, a difference between mouse experiments and potential clinical application. However, it may be possible to remove helper T cells from a human patient and stimulate them so that all the cells that recognize a given virus grow, Kamphorst says.

"This is an active area of research and several laboratories are looking at how best to stimulate T cells and re-introduce them," she says.

In addition, she and her co-workers are examining what types of hormones or signaling molecules the helper cells provide the killer cells. That way, that molecule could be provided directly, instead of cell therapy, she says.

The molecule PD-1 was previously identified by Ahmed and colleagues as a target for therapy designed to re-activate exhausted immune cells. Antibodies against PD-1 have been undergoing tests in clinical studies against hepatitis C and several forms of cancer.

Collaborators from Harvard Medical School/Dana Farber Cancer Institute contributed to the paper. The research was supported by the National Institutes of Health and the Cancer Research Institute.

Reference: R.D. Aubert et al. Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection. PNAS Early Edition (2011).

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

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>