Peter Wrighton-Smith, CEO of Oxford Immunotec, talks to Bioscience Today about growing understanding of the importance of T cells in protecting us from disease, as well as their critical role in measuring immune responses to infection.
The coronavirus (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has been responsible for many things, but perhaps one of the few positive outcomes of the pandemic is the unprecedented level of collaboration amongst the scientific community. Thanks to significant funding and a global urgency, some of the world’s foremost scientific minds came together to develop a collective understanding of the transmission, detection and protection against the novel coronavirus.
This global collaboration has had astounding results, including the rapid development of vaccines and an increased understanding of the significance of T cells in immune responses to viral infection and vaccination. This renewed interest in T cells may prove to be clinically significant in a variety of applications in the coming years. T cells are white blood cells, named such as they mature in the thymus, and they play a crucial role in orchestrating the immune response as well as directly destroying pathogens.
In the past, including in the early days of the pandemic, T cells were often overlooked as a monitoring device for the immune response in favour of antibodies. However, the extensive research carried out into immune responses to SARS-CoV-2 demonstrated the limitations of antibodies and the importance these T cells have in protecting us from disease, as well as the critical role that they can play in measuring immune responses to infection. Recent evidence has demonstrated that the measurement of T cells can provide valuable information about the ability of individuals to mount an effective, durable immune response following natural infection or vaccination.
For example, studies have shown that when detecting adaptive immune responses to SARS-CoV-2 infection, T cell testing may offer a more robust analysis than serology tests. Serology testing detects antibodies, indicating past exposure, but antibodies may weaken over time and some individuals have been shown to not develop antibodies at all.
On the other hand, T cell detection identifies SARS-CoV-2 specific T cells in the majority of PCR-positive cases and also picks up some individuals who test negative by serology. SARS-CoV-2 specific T cell responses may also be longer-lasting than antibodies, and thus may provide valuable information on the longevity of immune responses. Further, T cells have been shown to be more resistant to the mutations that occur in COVID-19 variants of concern, meaning that T cells may prove to be a more accurate measure of durable protection as the virus continues to mutate.
Antibodies and T cells both have a complementary function in the immune system, representing two different but complementary sides to humans’ adaptive immune response.
When exposed to a new infection, both B and T cells are activated. B cells result in the production of antibodies, while T cells differentiate into one of two types: helper T cells which have several functions, including assisting B cells with the production of antibodies; and cytotoxic T cells, which fight viral infections.
The role of T cells in the immune system is becoming more widely understood, but it’s already clear they have an important part to play in a number of clinical functions. For example, T cells play a central role in infectious diseases like tuberculosis or viral infections like COVID-19. They are also important in transplantation where their role is complex, as they’re necessary for fighting off infections but can also be involved in transplant rejection.
In the field of immune oncology T cells are central to the body’s ability to regulate cancer. Conversely, in autoimmune diseases, T cells’ regulation malfunctions as the immune system mistakenly attacks the body.
As science uncovers more about T cells, it is no understatement to say that the importance of measuring T cells is becoming more widely recognised across drug and vaccine development, diagnosis, prognosis and monitoring of different clinical conditions.
However, mainstream clinical use has been limited to date, as measuring T cells has several technical challenges that have restricted its widespread adoption. Two key requirements have been particularly difficult to overcome. Firstly, measuring T cells requires a very sensitive methodology, as the specific T cells that need to be measured can be extremely rare. Secondly, T cell tests measure T cell function, so live cells are needed.
As a result of these factors, T cell tests have historically been challenging to perform in the lab. They have been largely manual and complex procedures with expertise needed to isolate the T cells required and handle them without disrupting their function. The logistics of sample handling has also presented difficulties, as cells need to be alive when they reach the lab, and typically require processing very soon after arrival, which makes it difficult to fit the tests into routine and large-scale applications.
Our focus over the past 20 years has been to make working with T cells much simpler and easy to perform while maintaining the exceptional sensitivity required to obtain accurate, reproducible results. We have invented and pioneered a number of technologies which have been developed to overcome these key challenges.
The first has been improvements to the highly sensitive ELISPOT technique, which isolates T cells and interrogates them in vitro (with specially designed peptide pools) to identify those rare T cells which produce the tell-tale chemical messenger (IFN-gamma) in response, identifying them as being specific for the infection. Once complete, the test readout is a number of spots in a well of a microtiter plate – each one representing just one of those rare T cells – which can simply be counted to indicate the test result.
This process has been simplified into Oxford Immunotec’s T-SPOT® technology platform, making the test easier to run in a standard routine laboratory. The recent introduction of automation to this procedure has simplified the process further, and reduced the labour and expertise required to run the test – making large scale trials and routine clinical use more tractable. The same technology used to allow automation also enables the extension of sample stability, so there is more time for samples to arrive at the lab, significantly expanding the geographical catchment for samples. This and the potential for sample batching, also streamlines integration into the laboratories’ existing procedures.
We and others will continue to invest in developing these tests further, making the most sensitive of assays even more automated and even more simple to run. Combine this with the continued increase in our understanding of the role of T cells in infection and in immunity against infection, and it is clear that the use of T cells will become more widespread, particularly in vaccine development and in understanding immunity in a wide range of infectious diseases in 2022 and beyond.
Dr Peter Wrighton-Smith
Chief Executive Officer and founder of Oxford Immunotec
Oxford Immunotec is a global, high-growth diagnostics company and part of the PerkinElmer group. Oxford Immunotec is uniquely placed as the only company in the world offering regulated ELISPOT assays for T cell measurement. Since 2002, Peter has led Oxford Immunotec from the foundation stages, through product development to regulatory approval in over 50 countries, and subsequent worldwide commercialisation. Peter has a Masters in Engineering, Economics & Management, and a Doctorate in Medical Engineering both from Oxford University.