Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The tricks of the immune system: How the T-cell response changes in chronic virus infections

23.06.2020

More than half of the world's population is infected with the cytomegalovirus. The majority of people don't even notice the infection, since their immune systems keep the virus in check. Groups of T cells with a variety of virus-specific receptors play a key role in this process. Now researchers at the Technical University of Munich (TUM) have analyzed their interactions in detail for the first time. The results could be useful for future therapies against infections and cancer.

"The COVID-19 pandemic clearly demonstrates the importance of understanding how the immune system reacts to virus infections," says Dr. Kilian Schober.

Together with an interdisciplinary team of researchers from Medicine, Biology and Bioinformatics, he is investigating how important agents in the body's immune system known as T lymphocytes or T cells react when a cytomegalovirus invades the organism and how the immune response changes when the infection becomes chronic.

The team was able to show that the T cell response is a dynamic process and published their findings in the journal Nature Immunology. Different T cells with different receptors are especially active in various phases of the virus infection.

"The discovery of this change over time was a big surprise to us," says Schober, the lead author of the study. Until now scientists assumed that after an infection primarily those defense cells multiplied that are especially good at docking onto the cell structures impacted by the virus.

As a result it was assumed that in a chronic infection the number of these highly specialized "killer" cells remained permanently increased. But the new research results show a reversal in selection: The longer the infection lasts, the lower the average binding strength of the T cells.

The secret of reverse selection

In order to monitor the T cell response over the course of an infection, the team led by Prof. Dirk Busch, director of the TUM Institute for Medical Microbiology, Immunology and Hygiene, analyzed blood samples from people who carry the cytomegalovirus. This very widespread virus, from the family of herpes viruses, is found in more than half the world's population.

The majority of those infected have no symptoms, but the virus can trigger infections of the lungs or the liver in patients with weaker immune systems. In the majority of cases the time of infection in humans is unknown and remains unnoticed for several years.

Therefore, the team also conducted laboratory investigations of the blood of mice infected with the cytomegalovirus where the date of the initial infection was known.

The team used a procedure it developed itself to isolate and analyze the defense cells. Every person has millions of different T cells, each with an individual protein complex on its surface. The structure of this T cell receptor (TCR) determines which virus structures it can dock onto and how firmly it will adhere.

The result of the complex investigation: Immediately after an infection with cytomegalovirus, T cells with strong bonding receptors dominate. After some time however almost exclusively the weaker-bonding receptors are found in the blood.

Prof. Busch emphasizes the fact that we can only speculate about the possible benefits of this reverse selection: "We assume that the modified immune reaction protects the organism from an excessive immune system reaction." He adds that a long-term secretion of cytokines by T cells with high binding affinity can trigger strong inflammation and thus harmful side-effects.

Important findings for infection and cancer therapies

"These findings are particularly exciting in the context of therapeutic application. T cells have been used successfully as 'living drugs' for over 25 years. Our findings suggest that in cases of chronic immune responses, T cells with weaker binding receptors are longer-lived," says Prof. Busch, adding that in the future the results could help improve T cell therapies used to fight infectious diseases and tumors.

More information:

The research received funding from the DZIF German Center for Infection Research and the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG)) (CRC 1321/TP17; CRC 1054/B09 and CRC 1371/TP04).

Wissenschaftliche Ansprechpartner:

Prof. Dr. med. Dirk H. Busch
Technical University of Munich
Institute for Medical Microbiology, Immunology and Hygiene
+49 89 4140-4120
dirk.busch@tum.de
http://www.mikrobio.med.tu-muenchen.de/

Originalpublikation:

Kilian Schober, Florian Voit, Simon Grassmann, Thomas R. Müller, Joel Eggert, Sebastian Jarosch, Bianca Weißbrich, Patrick Hoffmann, Lisa Borkner, Enzo Nio, Lorenzo Fanchi, Christopher R. Clouser, Aditya Radhakrishnan, Lorenz Mihatsch, Philipp Lückemeier, Justin Leube, Georg Dössinger, Ludger Klein, Michael Neuenhahn, Jennifer D. Oduro, Luka Cicin-Sain, Veit R. Buchholz and Dirk H. Busch: Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection. Published in: Nature Immunology, March 16, 2020. DOI: 10.1038/s41590-020-0628-2
https://www.nature.com/articles/s41590-020-0628-2

Dr. Ulrich Marsch | Technische Universität München
Further information:
http://www.tum.de/die-tum/aktuelles/

Further reports about: T cells T-cell response immune system virus infections

More articles from Life Sciences:

nachricht Catalyzing a green future
23.06.2020 | King Abdullah University of Science & Technology (KAUST)

nachricht New approach for a biological programming language
23.06.2020 | Technische Universität Graz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Virtually Captured

Biomechanical analyses and computer simulations reveal the Venus flytrap snapping mechanisms

The Venus flytrap (Dionaea muscipula) takes only 100 milliseconds to trap its prey. Once their leaves, which have been transformed into snap traps, have...

Im Focus: NASA observes large Saharan dust plume over Atlantic ocean

NASA-NOAA's Suomi NPP satellite observed a huge Saharan dust plume streaming over the North Atlantic Ocean, beginning on June 13. Satellite data showed the dust had spread over 2,000 miles.

At NASA's Goddard Space Flight Center in Greenbelt, Maryland, Colin Seftor, an atmospheric scientist, created an animation of the dust and aerosols from the...

Im Focus: Researchers create a photographic film of a molecular switch

Molecular switches are the molecular counterparts of electrical switches and play an important role in many processes in nature. Nanotechnologist now produced a photographic film at the atomic level and thus tracked the motion of a molecular building block. The result was a light-controlled "pedalo-type motion", going forward and backward. The study has been published in the "The Journal of Physical Chemistry Letters".

Molecular switches – they are the molecular counterparts of electrical switches and play an important role in many processes in nature. Such molecules can...

Im Focus: Al2Pt for oxygen evolution reaction in water splitting: a strategy for creating multi-functionality in electrocatalysis

The inter-institutional MPG-consortium MAXNET Energy integrated the scientists from different institutions in Germany and abroad. As a result of close and fruitful collaboration within this framework, the scientists from Chemical Metal Science department at MPI CPfS together with experts from Fritz Haber Institute in Berlin and MPI CEC in Mülheim an der Ruhr, developed a new concept for producing multifunctionality in electrocatalysis and successfully illustrated it with an example of intermetallic compound Al2Pt as precursor for OER electrocatalyst material.

The transition from fossil fuels to renewable energy sources strongly depends on an availability of effective systems for energy conversion and storage.

Im Focus: The smallest motor in the world

A research team from Empa and EPFL has developed a molecular motor which consists of only 16 atoms and rotates reliably in one direction. It could allow energy harvesting at the atomic level. The special feature of the motor is that it moves exactly at the boundary between classical motion and quantum tunneling - and has revealed puzzling phenomena to researchers in the quantum realm.

The smallest motor in the world - consisting of just 16 atoms: this was developed by a team of researchers from Empa and EPFL. "This brings us close to the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Dirac electrons come back to life in magic-angle graphene

23.06.2020 | Materials Sciences

Catalyzing a green future

23.06.2020 | Life Sciences

New design for 'optical ruler' could revolutionize clocks, telescopes, telecommunications

23.06.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>