Battling infections using trapped immune cells

Research has revealed how immune cells stay trapped within the lungs. This could help improve the development of better vaccines, which focus on generating local immunity. Most immune cells in the blood travel through the body, searching for inflamed tissue. However, the lungs contain very effective immune cells locally. These local habitants are specialized in eliminating viruses and bacteria that reside within the lungs. Scientists of Sanquin and their Australian colleagues have shown how these cells stay trapped within the lungs. They publish this work in Science on 22 April 2016.

Resident T-cells, which are specialized immune cells, are very important for an optimal immune response. These cells are located within organs like the lungs and have only recently been discovered. “We always thought that T-cells returned to the blood after eliminating a virus, like the flue” says Klaas van Gisbergen, a group leader at Sanquin. “That’s where you normally find immune cells that travel to the next infection”. So why are certain T-cells trapped within the tissue? Van Gisbergen and his group compared Tcells in blood to resident T-cells in tissue using an experimental infection model. “We discovered that T-cells that were trapped in tissue started making the protein Hobit. Hobit is able to stop certain processes within the cell ensuring the cell is not able to move: it stays trapped within the tissue. This is very convenient for our immune system, because the next time a virus like the flue comes back, the anti-flue T-cells are already in the lungs, where they are needed most”.

Local protection

Van Gisbergen also encountered these resident T-cells in the skin, liver and gut. All these T-cells express the protein Hobit. Hobit also ensures that these T-cells stay trapped within these organs, where they were first activated. For this reason these cells are specialized in the immune response against local infections. Van Gisbergen: “We have discovered that T-cells in these organs strongly differ from each other. They adjust to the surrounding tissue. This makes them even more effective.” The T-cells in these organs are ready throughout their entire life. Because of their memory they are optimally prepared to eliminate pathogens upon entry. Vaccination also uses the memory of the immune system. After vaccination we develop immunity for a prolonged time, sometimes even the rest of our lives. “We could even be better protected if it’s possible to develop vaccines that encourage the production of resident T-cells” postulates Van Gisbergen. “Knowing that Hobit plays an important role brings us closer to the development of powerful vaccines”.

Publication

Mackay LK, Minnich M, Kragten NA, Liao Y, Nota B, Seillet C, Zaid A, Man K, Preston S, Freestone D, Braun A, Wynne-Jones E, Behr FM, Stark R, Pellicci DG, Godfrey DI, Belz GT, Pellegrini M, Gebhardt T, Busslinger M, Shi W, Carbone FR, van Lier RA, Kallies A, van Gisbergen KP. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 2016; 352(6284):459-63.