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!
The genes are not to blame
20.07.2018 | Technische Universität München
Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Materials Sciences
20.07.2018 | Physics and Astronomy
20.07.2018 | Materials Sciences