Cytotoxic T lymphocytes

Published on July 28, 2021   33 min

Other Talks in the Series: The Immune System - key concepts and questions

Hello, I'm Gillian Griffiths and I'm the Professor of Immunology and Cell Biology at the University of Cambridge in the UK. I'm going to give a talk today about cytotoxic T lymphocytes.
Cytotoxic T lymphocytes are incredibly important cells for the immune system, because they kill virally infected and cancerous cells, and they do so remarkably effectively. You can see that in this little video here, where the cytotoxic T lymphocyte is labelled with its actin cytoskeleton in orange, and we can see it as it attacks the cancerous cell, where the membrane has been marked with a blue marker. They are very good and very effective, and this has had very important medical consequences recently.
New therapies that have harnessed the power of these cytotoxic T-cells have led to remarkable breakthroughs in cancer treatments. What I would like to try and outline in this lecture, is how much we know about how cytotoxic T lymphocytes work, and explain to you how this is being harnessed in immunotherapies.
If I were to give a very short history of cytotoxic T lymphocytes, I would outline advances that were made in each of these decades. In the 1950s, cytotoxic T lymphocytes were initially investigated to understand graft rejection, and it wasn't until the 1960s that it was realised that these were sensitised lymphoid cells that could be found to lyse target cells. In the 1970s it was found to be T-cells that were responsible for cytotoxicity, and in fact, there were some remarkable videos which showed these little cells as serial killers, destroying one target after another. This moved into a molecular age in the 1980s, where the cytolytic proteins were identified, and they were all found to be packaged in little granules that could be released when the cytotoxic T lymphocyte met its target. The key proteins in this process were found to be perforin (which was initially called 'cytolysin'), and a series of granzymes, which stood for 'granule-contained enzymes'. Then in the 1990s, the therapeutic side of these came to the fore as CAR-T cells (chimeric antigen-receptor T-cells) were shown to be able to treat some blood cancers. It's come on yet further, as I will explain, with checkpoint inhibitors in the following years.