Researchers rejuvenate immune system
Blood-forming stem cells are key to a strong immune defence

Ulm University

One side effect of getting older is a weakening immune system. This not only makes seniors more susceptible to infections. Vaccinations - against the flu, for instance - become also less effective. Scientists in Ulm led by Professors Hartmut Geiger and Reinhold Schimbeck have now found a way to rejuvenate the body's defence system in a mouse model: The key to this are blood-forming stem cells. The authors furthermore demonstrated the important role of these stem cells in the ageing of the immune system. Their findings, published in the renowned science journal 'Blood', could contribute to a healthier way of ageing as well as better vaccination outcomes for senior citizens in the future.

When we age, our immune system ages with us. The involution of the thymus gland, an organ known to produce important immune cells, was long thought to be the main culprit. Now, however, a group of immunologists and stem cell researchers in Ulm are shining a spotlight on another protagonist: blood-forming stem cells. They are the body's 'maintenance service provider' and in charge of the regeneration of blood and immune cells, among other things.

However, just as the rest of the organism these stem cells lose their performance capacity with age and have a harder time keeping up with their 'repair mandate'. Ulm's stem cell researcher Professor Hartmut Geiger has shown in the past that blood-forming stem cells shift to a different signalling system as they age, which creates chaos in the 'maintenance operations'. With the help of the pharmacological substance Casin it is possible, however, to reverse this process so that the blood-forming stem cells return to functioning as they did in younger years.

For their current publication, the scientists used a novel bone marrow transplantation model to study how the ageing of blood-forming stem cells actually affects the performance of the immune system. For this purpose, they isolated bone marrow stem cells of older and younger mice. Some of the older cells were then exposed to Geiger's 'rejuvenation treatment'.

In a second step, the old, the young and the rejuvenated blood-forming stem cells were transplanted into transgenic mice without immune system. Only twelve weeks later, the researchers were able to assess the competence of the immune systems that had developed after the transplants. One aspect they looked at was the vaccination response. 'Vaccination is the process of administering innocuous variants of pathogens, which causes the immune system to build defence cells. In the event of an infection, these pre-existing immune cells then help to swiftly respond to bacteria or viruses. The vaccination response can therefore provide information on the functionality of the body's defence,' explains Dr. Hanna Leins, first author and academic staff member at the Institute of Molecular Medicine.

With their model the researchers demonstrated the successful rejuvenation of blood-forming stem cells and consequently the immune system: The vaccination response of the young immune system and the immune system that evolved from rejuvenated stem cells proved to be equally strong. As expected, the defence system in the mice that received old stem cells showed a much weaker response to the vaccination.

'All in all, our findings demonstrate the important role of blood-forming stem cells in the ageing of the immune system. When those stem cells get old, the defence system cannot regenerate adequately. The organism becomes increasingly susceptible to infections,' says Professor Reinhold Schirmbeck, group leader at the University Clinic for Internal Medicine I. 'Our model also shows that we can turn the clock back: The rejuvenation of aged stem cells can restore the immune competence in senior years,' adds stem cell expert Professor Hartmut Geiger, Director of the Institute of Molecular Medicine at Ulm University.

The group's findings result in a better understanding of the ageing immune system and show that the performance capacity of the body's defence is largely dependent on blood-forming stem cells. In the long run, these new findings could contribute to a healthier way of ageing and improve the success rates of vaccines or immune therapies for cancerous diseases in elderly people. The journal 'Blood' rated this research work as one of the best publications of 2018.

This publication is the result of an interdisciplinary collaboration of Ulm University and its Medical Centre (Internal Medicine I, Institute of Molecular Medicine) together with the geriatric Agaplesion Bethesda Clinic in Ulm (Professor Michael Denkinger). The researchers received funding through the research alliance SyStaR of the Federal Ministry of Education and Research (BMBF). The German Research Foundation (DFG) supported the group via the research training group CEMMA (Cellular and Molecular Mechanisms in Aging).

Hanna Leins, Medhanie Mulaw, Karina Eiwen, Vadim Sakk, Ying Liang, Michael Denkinger, Hartmut Geiger and Reinhold Schirmbeck: Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood 2018 132:565-576; doi:

Text and media contact: Annika Bingmann

Researchers of Ulm University and its Medical Centre rejuvenate the immune system (from the left): Prof. Hartmut Geiger, Dr. Hanna Leins, Prof. Reinhold Schirmbeck and Juniorprof. Medhanie Mulaw (photo: Andreas Brown)
Measurements of vaccination responses via ELISPOT. The number of (blue) spots reflects the strength of the immune response. (photo: Andreas Brown)