During our life-time, we encounter many pathogens (infectious agents like viruses). The immune system is our main defence mechanism to prevent us from getting sick. One of the key players is adaptive immunity (including T cells), which gets its name from is ability to change and adapt depending on the pathogen you encounter. T cells detect and clear these pathogens in a highly specific manner. In other words, when you get infected with an influenza virus your adaptive immune system comes into action, but only activates those immune cells that are able to recognise this particular influenza virus strain. The initial response upon the first encounter with a pathogen is relatively slow. An important feature of the adaptive immune system is that it remembers the pathogen you encountered. This immunological memory enables your immune system to respond faster and stronger when you get re-infected with the same pathogen. This way your immune system prevents you from getting sick a second time. It is not fully understood how our immune response develops (children), maintains (adults) and loses (elderly) memory and strong functionality over the years.
TC-Evo’s overarching aim: To gain fundamental knowledge on how our immune system develops during immunologically-distinct phases of our life, from birth to old age.
Tc-Evo focuses on a specific part of the adaptive immune system, the so called CD8 T cells, also known as killer cells. Killer T cells have special receptors on their cell surface, the T cell receptors (TCRs), which enables them to recognise virus infected cells in a highly specific manner. Once they recognise an infected cell, they can kill this cell before it makes new viruses that could infect other cells (Figure 1). Previous research on killer T cells mainly focused on their function in adults (adults are known to have excellent and very specific killer T cells), and some studies were done in elderly. However, research that focuses on how these killer T cells develop during childhood are non-existent. Studying the killer T cell response in children is of special interest as children cope exceptionally well with novel virus infections. Not only are children able to form a strong memory response, their ability to recover from novel virus infections is superior to that of other age groups (Figure 2).
The first part of the Tc-Evo project took place at the University of Melbourne in Australia and focused on answering the overarching aim of this project using the most recent and ground-breaking technology to study killer T cell responses in the greatest detail as possible.
The second part of the Tc-Evo project took place at Sanquin in the Netherlands. The aim of this second part was to implement this new ground-breaking technology at a European research institute, while focusing on a slightly different cell type. Due to COVID-19, this part was revised to study COVID-19 specific immunity after infection and vaccination in high-risk groups including autoimmune patients.
Importance: Fundamental knowledge on how or immune system develops while ageing is especially relevant given our ageing population and is likely to contribute to new therapies against a wide variety of diseases. Furthermore, the Tc-Evo research project is likely to give new insights on how to develop new vaccines strategies that train our immune system to develop stronger localised immune memory response while retaining some flexibility in order to cope with new/slightly different pathogenic infections. For example, a single vaccine that gives long-lasting protection against seasonal and pandemic viruses.
