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If you could start off by introducing yourself and what you do at the Doherty Institute.

I am Carolien van de Sandt and I am a Postdoctoral Researcher in the Department of Microbiology and Immunology in the Kedzierska laboratory.

I am originally from the Netherlands and I undertook my PhD at the University of Rotterdam studying immunity against influenza viruses and more specifically the so called CD8 “killer” T cells.

What brought you to the Doherty Institute? 

My PhD focused on basic immunology and virology, understanding the interaction between the virus and the immune system, if and how the immune system can recognize multiple influenza strains and how viruses escape from the immune response. However, I was very keen to understand why people respond differently to viral infections, especially across different age groups. School-aged children tend to respond really well to a range of viruses, but very young children can get quite sick. The same when you get older, after the age of 65 you have a higher chance of getting a severe infection from respiratory like influenza and COVID-19.

I always wanted to understand the logical reasons for this observation. Why is that old people are less able to cope with these infections while children seem to benefit from this superior immune response. That is why I joined the Kedzierska laboratory in 2018, to work on a human ageing project to study how CD8+ T cells developed across a human’s lifespan.

I want to not only understand how the immune system develops over time, but also how we can harness the optimal immune response to benefit all age groups.

You’ve just been awarded the 2022 Australian Research Council Discovery Early Career Research Award. Tell us about that.  

It’s a three-year grant valued $438,712 to continue my studies into understanding the aging process of the immune system.

In our previous study, we were able to show that the changing immune response was to do in part with T cell receptors expressed on the surface of CD8+ killer T cells. T cell receptors play an important role in recognising influenza virus infected cells. We were able to show that the composition of these receptors undergoes important changes as we age. The most optimal T cell receptors appear during early childhood, are maintained into adulthood, but begin to wane as you get older.

 I now want to look at where these optimal receptors come from and how these receptors get ‘educated’ to recognise infected cells and attack them. Is the reason we why we lose our ability to fight viruses as we get older, due to our inability to recognise them anymore?

We have set up a large cohort of human samples from people of all ages. We have core blood samples from umbilical cords, so babies who have never been exposed to the influenza virus and have completely naive immune systems; children who have first influenza virus infection; adults who have seen many infections; and elderly individuals.

The education process the T cell receptors go through happens in a special organ called the thymus. This organ teaches T cell receptors to recognise the difference between healthy ‘self’ cells and virus infected cells they need to attack.

In the coming years I will study if and how this teaching process changes over human lifespan, which could affect our body’s ability to combat influenza and other viral pathogens. Is the reason our immune system wanes, due to the fact we lose the ability to educate these receptors?

What to next?

My ultimate goal is to find a way to stimulate the optimum immune response we see in children and young adults so we can improve an individual’s immunity throughout their entire lifespan.

If you indeed lose your ability to train yourself, could there be a way to circumvent this? Can you maintain the previously trained cells for a longer period of time so you don’t lose you optimal immunity? Or is there a way to train them without the thymus?

We are just about to entering our fourth week of lockdown in Melbourne, any tips for getting through it?

Well I actually only recently got back from a year in the Netherland, where I spent almost the whole year in lockdown! And I arrived back in Melbourne just in time to go into this lockdown, so I have a bit of experience. I am lucky that for the most part I still get to go into work in the lab and see colleagues, so for me it’s the social interactions outside work I am really missing. But on the other hand, it is a good time to catch up on some of my hobbies for which I normally do not have much time, like painting and reading.