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T cells

What are T cells?

Our body contains many types of different immune cells. One of the key immune cell subsets that provides protection against viral infections and cancer are T cells. Viruses replicate by entering the cells of our body and reprogramming them so they make new viral particles. To counter viruses, every cell of the body continuously shows (`presents`) pieces of the proteins that it is producing on its cell membrane in specialized strcutures called HLA molecules. T cells patrol the body and scan the contents of HLA molecules on cell membranes. If they encounter an HLA molecule containing pieces of viral proteins, T cells mediate elimination of the infected cell. In addition, T cells produce cytokines; immunological hormones which recruit other immune cells that mediate inflammation and contain the infection. Killing of infected cells is mediated by CD8+ T cells, also called cytotoxic T cells. Production of cytokines that recruit and activate other cells is mostly mediated by CD4+ T cells, also called helper T cells.

T cell activation

In contrast to cells of the innate immune system, T cells are not immediately ready to start killing and first need to be activated (`primed`). The total T cell pool has the capacity to detect an enormous number of different pathogens, because it consists of millions of different cells, each with its own capacity to recognize a specific pathogen-derived protein. However, each cell is in a dormant (`naïve`) state and by itself incapable of generating a sufficient response. Upon infection, the few T cells specific for this virus must therefore first replicate (proliferate) to form an army of millions of cells which together are capable of fighting the infection. In addition, T cells must be `armed`, meaning that they start producing the molecules with which they mediate their function. T cell activation is a complex process that involves many different immune cells and cytokines and takes place in lymph nodes. After priming, naïve T cells have become effector T cells, leave the lymph node and migrate to the site of infection to mediate their anti-viral effect. In addition, some specialized CD4 T cells remain in the lymph node where they help B cells to produce antibodies.

T cell memory

Together with B cells that produce antibodies, T cells are part of the adaptive immune system. This means that they are responsible for providing immunity; long term protection against re-infection with the same virus. This long-term protection is mediated by so called immunological memory cells. After a virus has been eliminated from the body, the majority of the effector cells dies through a well-regulated process. A small number of cells remains as memory cells. These memory cells already produce the proteins they need to fight infection and therefore don`t need priming. In addition, through rapid proliferation they are able to generate a new, active army of cells in a much shorter time than naïve cells. Therefore, these cells are usually able to quickly eliminate the re-encountered virus, without the infected person to have any symptoms of disease.

T cells at the center of excellence for Virus Immunology and Vaccines

Clearly, T cells are very important in our fight against viral infections and a vaccine is only efficient if it also induces a proper T cell response. At the same time, viruses try to prevent proper activation of T cells and use insidious strategies to avoid recognition by these immune cells. At our center, we therefore study several aspects of T cells in the context of viral immunology and vaccines. We study the way in which T cells are primed and how they form efficient memory. We study how the virus manipulates anti-viral processes in the cell to avoid recognition by T cells and we develop strategies to counter these processes. Finally, we are developing advanced vaccines that improve T cell activation and memory formation. T cell biology is therefore an important part of the work that we do.