The blood is the main source of studies on the immune system, despite the fact that most diseases are combated by immune cells in the body’s tissues. A new study from Karolinska Institutet and the University of Pennsylvania has identified which immune cells patrol the human body’s tissues and circulate back into the blood. The study, which is published in Cell, shows that not all T cells do this – some are found mostly in the blood where they constitute a unique part of our immune system.
The white blood cells known as T cells are a key part of the immune system. To search the body on the hunt for infections, such as viruses and different forms of cancer, they migrate from the blood out into other tissues and back again, constantly recirculating.
Different T cells operate in different ways. Some of them are called killer T cells, CD8+, and are mainly associated with their ability to kill virally infected cells or tumours.
More research is needed to better understand the role played by recirculation in the human defence system. Researchers at Karolinska Institutet and the University of Pennsylvania, USA, have now studied which immune cells migrate under normal conditions from tissues to blood in humans.
The researchers have analysed blood, various organs and lymphatic fluid, which transports immune cells. The lymph they extracted from the thoracic duct, which is the largest lymph duct and which collects lymph from the legs, pelvis, abdomen, left arm, the left side of the thorax, the throat and the head.
Killer T cells
Their results confirm previous studies on animals that identify T cells as the most common immune cell type that recirculates between blood and other tissue.
“It turns out that killer T cells differed considerably between the blood and the lymph,” says the paper’s first author Marcus Buggert, assistant professor at the Department of Medicine, Karolinska Institutet (Huddinge). “Doing a range of tests we were able to show that such T cells with the most prominent ‘killer instinct’ are mainly found in the blood and do not recirculate under normal conditions. This means that many of the T cells that we’ve spent all these years studying might play a smaller part in our defence against intruders than we once thought.”
This is just one of several studies showing that T cells in the blood are different to those in other tissues.
“These results suggest that studies of immune cells in the blood, especially when it comes to current research on COVID-19, can’t be translated to what happens in the rest of the body when the virus spreads,” says Dr Buggert.
Since the study identifies what type of T cell can migrate between blood and other tissue, the results can be valuable to different ongoing clinical experiments with modified T cells.
Tailor T cells
“Theoretically speaking, we can now tailor T cells able to effectively migrate to tissue and thus improve the effect of immune therapies for solid tumours, auto-immune diseases and latent infections, such as HIV,” he continues. “Just how we can achieve this and discover the actual function of killer T cells in body tissue is the next question we’ll try to answer.”
The study is one of the first of its kind on humans with animals as the control group.
The study was financed by the Swedish Research Council, Karolinska Institutet, the Swedish Society for Medical Research, the Jeansson Foundations, the Åke Wiberg Foundation, the Swedish Society of Medicine, the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Magnus Bergvall Foundation, the Lars Hierta Foundation, the Doctors against AIDS Research Fund, the Jonas Söderqvist Foundation and the Clas Groschinsky Memorial Foundation. There are no reported conflicts of interest.
“The identity of human tissue-emigrant CD8+ T cells“. Marcus Buggert, Laura A. Vella, Son Nguyen, Vincent Wu, Zeyu Chen, Takuya Sekine, André Perez-Potti, Colby R. Maldini, Sasikanth Manne, Samuel Darko, Amy Ransier, Leticia Kuri-Cervantes, Alberto Sada Japp, Irene Bukh Brody, Martin A. Ivarsson, Jean-Baptiste Gorin, Olga-Rivera Ballesteros, Laura Hertwig, Jack P. Antel, Matthew E. Johnson, Afam Okoye, Louis Picker, Golnaz Vahedi, Ernesto Sparrelid, Sian Llewellyn-Lacey, Emma Gostick, Johan Sandberg, Niklas Björkström, Amit Bar-Or, Yoav Dori, Ali Naji, David H. Canaday, Terri M. Laufer, Andrew D. Wells, David A. Price, Ian Frank, Daniel C. Douek, E. John Wherry, Maxim G. Itkin, Michael R. Betts. Cell, online 10 December 2020, doi: 10.1101/2020.08.11.236372.