Transfer of a few immune cells can protect immunodeficient patients

June 17, 2014
As work with cells requires highly-pure working conditions, the scientists wear sterile clothing in the clean rooms. Credit: M. Neuenhahn / TUM

When patients have to undergo a bone marrow transplant, the procedure weakens their immune system. Viruses that are usually kept in check in a healthy immune system may then cause potentially fatal infections. Scientists at Technische Universität München, together with colleagues from Frankfurt, Würzburg and Göttingen, have now developed a method which could offer patients conservative protection against such infections after a transplant. The method has already been used to treat several patients successfully.

The of the human immune system are created from special stem cells in the bone marrow. In diseases affecting the , such as leukemia, the degenerate cells must be destroyed using radiation or chemotherapy. Subsequently, the hematopoietic system has to be replaced with stem cells from the blood of a healthy donor. Because of the resulting temporary weakening of the immune system, patients are more exposed to viruses that would normally be warded off.

The cytomegalovirus (CMV), which can cause serious damage to lungs or liver in persons with a weakened defense, poses a major clinical problem. In healthy human beings, a CMV infection will usually not produce any symptoms, since the virus is kept at bay by specific . In their work, the scientists were able to demonstrate that the transfer of just a few specific immune cells is sufficient to protect the recipient with the weakened against infections. To do this, they used T cells that can recognize and kill specific pathogens.

Tested in an animal model

Dr. Christian Stemberger, first author of the study, and his colleagues, first isolated T cells from the blood of healthy donor mice. These immune cells were directed against molecular elements of a bacterial species which normally causes severe infections in animals. The T cells were then transferred to recipient mice that, due to a genetic modification, could no longer produce immune cells of their own – similarly to patients suffering from leukemia.

Following the T cell transfer, the researchers infected the treated recipient mice with the bacteria. The results showed that the animals now have effective immune protection against the pathogens, preventing them from becoming ill. "The most astonishing result was that the offspring cells of just one transferred donor cell were enough to completely protect the animals," Christian Stemberger explains.

Successfully used in patients

Finally, the scientists used virus-specific T cells to treat two critically ill patients. Due to a congenital immunodeficiency and leukemia, respectively, stem cell transplants had to be performed on the two patients. Weakened by the procedure, both patients developed CMV infections.

Using a new method, the scientists therefore isolated T cells specifically programmed to target the CMV virus from the blood of the donor and transferred small numbers of these cells to the . After only a few weeks, the virus-specific cells proliferated. At the same time, the number of viruses in the blood dropped. "It is a great advantage that even just a few cells can provide protection. This means that the cells can be used for preventive treatment in low doses that are gentler on the organism," Dr. Michael Neuenhahn, last author of the study, explains.

The potential of the identified T cells will now be examined in a clinical study. In addition to an innovative method for cell purification, scientists also have at their disposal a new TUM facility for the sterile manufacture of cell products. In TUMCells, cells can be produced in highly-pure conditions, in so-called clean rooms. In the future, the scientists want to use recent results and TUMCells to develop innovative cell therapies.

Explore further: Scientists use stem cells to create HIV resistance

More information: Christian Stemberger, Patricia Graef, Marcus Odendahl, Julia Albrecht, Georg Dössinger, Florian Anderl, Veit R. Buchholz, Georg Gasteiger, Matthias Schiemann, Götz U. Grigoleit, Friedhelm R. Schuster, Arndt Borkhardt, Birgitta Versluys, Torsten Tonn, Erhard Seifried, Hermann Einsele, Lothar Germeroth, Dirk H. Busch and Michael Neuenhahn, Lowest numbers of primary CD8+ T cells can reconstitute protective immunity upon adoptive immunotherapy, Blood, 2014. DOI: 10.1182/blood-2013-12-547349

Related Stories

Scientists use stem cells to create HIV resistance

June 10, 2014
(Medical Xpress)—Yuet Wai Kan of the University of California, San Francisco and colleagues have created HIV-resistant white blood cells by editing the genomes of induced pluripotent stem cells. The researchers inserted ...

Lipids help to fight leukemia

June 16, 2014
T cells use a novel mechanism to fight leukemia. They may recognize unique lipids produced by cancer cells and kill tumor cells expressing these lipid molecules. A study conducted by researchers at the University of Basel ...

Novel drug prevents common viral disease in stem-cell transplant patients, study finds

September 25, 2013
A new drug can often prevent a common, sometimes severe viral disease in patients receiving a transplant of donated blood-making stem cells, a clinical trial led by researchers at Dana-Farber Cancer Institute and Brigham ...

One cell's meat is another cell's poison

May 30, 2014
As a new therapeutic approach, Janus kinases are currently in the limelight of cancer research. The focus of interest is the protein JAK2. By inhibiting this protein one tries to cure chronic bone marrow diseases, such as ...

Immune cells regulate blood stem cells

February 21, 2014
Researchers in Bern, Germany, have discovered that, during a viral infection, immune cells control the blood stem cells in the bone marrow and therefore also the body's own defences. The findings could allow for new forms ...

Recommended for you

Manipulating a type of brain cell gets weight loss results in mice

July 28, 2017
A new study has found something remarkable: the activation of a particular type of immune cell in the brain can, on its own, lead to obesity in mice. This striking result provides the strongest demonstration yet that brain ...

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.