Cytotoxic T cell

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Cytotoxic T cells ( cytotoxic T lymphocytes , CTL, obsolete: T killer cells) belong to the group of T lymphocytes (T cells) and are part of the adaptive immune system . Their main task is to recognize and eliminate infected body cells using antigens typical of the pathogen . In addition, they play a role in combating degenerate cells .

Cytotoxic T cells are formed in the bone marrow , but they take an important development step in the thymus . There the generation of your individual T-cell receptor as well as a positive and negative selection takes place. This step ensures that the cells are able to recognize foreign antigens on the one hand and to ignore the body's own antigens on the other.

Functions

Cytotoxic T cells patrol the blood, lymphatic system , tissues and organs. In doing so, they constantly interact with the different, endogenous cells, check their condition and kill those that have been attacked and modified by pathogens. In addition to fighting infected cells, they also play a role in eliminating cancer cells.

At the molecular level, infected or degenerate cells are differentiated from healthy cells with the help of the T cell receptor on the side of the cytotoxic T cells and the MHC-I protein on the target cell side: MHC-I proteins are on the surface of all of them nucleated, endogenous cells. Antigen peptides are bound to them, which originate from the interior of the respective cell and which originate from the proteasomal breakdown of larger protein molecules. Healthy, uninfected body cells thus present a variable mixture of the most varied, cell-specific self-peptides. As a result, they identify themselves to the cells of the immune system as "healthy". If, on the other hand, they are infected by a virus, virus-specific antigen peptides also reach the MHC molecules and thus signal the immune cells that the target cell is infected . The T-cell receptors are located on the outside of the membrane of the cytotoxic T-cells and are characterized by the fact that they only bind one specific antigen. All T cell receptors on the surface of a cytotoxic T cell are specific for a single, specific antigen. Antigens which do not correspond to the specificity of the cytotoxic T cell are not recognized by it. If the activated cytotoxic T cells bind to their specific MHC-I peptide complex in the tissue, they release perforins and granzyme , which kill the bound target cell. In addition, activated cytotoxic T cells also produce and secrete proteins such as interferon-γ , which promotes the expression of MHC-I proteins in neighboring cells. This leads to an increased presentation of intracellular degraded peptides. In the case of a cell infected with a virus, for example, this also increases the presentation of viral peptides, which in turn are recognized by specifically imprinted cytotoxic T cells. The immune response is strengthened, especially in the infected area. Cytotoxic T cells are therefore important mediators of the cellular immune response and aim to stop intracellular infections (especially caused by viruses) by destroying the infected cells by induced apoptosis .

In addition, cytotoxic T cells also play a crucial role in fighting tumor cells. Because, due to mutations and changes in expression, these often present a different antigen spectrum than healthy cells. If specific, tumor-associated antigens are presented on the MHC-I molecules of the cancer cells, cytotoxic T cells can also be able to lyse these . This mechanism is jointly responsible for spontaneous tumor regressions and is used in cancer immunotherapy , for example in adoptive T cell transfer or dendritic cell vaccination.

development

During the development process of the T cells in the thymus , a large number of cytotoxic T cells with different specificities are generated. However, only those T cells that bind foreign but not endogenous peptides survive the selection process. This selection process drives about 95% of immature T cells into programmed cell death, at the end of the process there are naive cytotoxic T cells. The selection process in the thymus, but also other peripheral control mechanisms, ensure that no activated cytotoxic T cells are created that attack the tissue of the own organism and thus trigger autoimmune reactions. In order to generate activated and thus fully functional cytotoxic T cells, the antigen-specific interaction of the naive cytotoxic T cells with professional antigen-presenting cells (mostly mature dendritic cells ) is essential. Mature dendritic cells are able to activate naive CD8 + cytotoxic T cells via costimulative signals. This enables the activated cytotoxic T cells to eliminate infected or degenerate tissue cells in an antigen-specific manner. However, in order to achieve complete functionality and also to be able to form memory cells, additional interactions with CD4 + T helper cells are absolutely necessary.

A characteristic molecular marker for cytotoxic T cells is the CD8 protein , which binds to the MHC-I molecules. Together with the actual T cell receptor, with CD3 molecules and ζ2 or ζ / η chains, it forms the T cell receptor complex.

Individual evidence

  1. ↑ Janeway Immunology, 7th Edition, Hardcover - September 17, 2009 by Kenneth M. Murphy, Paul Travers, Mark Walport
  2. ↑ Norbert Wagner, Gunther Dannecker: Pediatric Rheumatology . Springer, 2007, ISBN 978-3-540-32814-8 , pp. 18 .
  3. ↑ Janeway Immunology, 7th Edition, 2014 edition, by Kenneth M. Murphy, Paul Travers, Mark Walport, ISBN 3-662-44227-2
  4. ↑ Teresa Manzo, Helen E. Heslop, Cliona M. Rooney: Antigen-specific T cell therapies for cancer: Figure 1. In: Human Molecular Genetics. , S. ddv270, doi: 10.1093 / hmg / ddv270 .
  5. ↑ Sheng Zhang, Qing Wang, Beiping Miao: Dendritic Cell-Based Vaccine in the Treatment of Patients with Advanced Melanoma. In: Cancer Biotherapy & Radiopharmaceuticals. 22, 2007, p. 501, doi: 10.1089 / cbr.2007.354 .
  6. ↑ Benedita Rocha, Corinne Tanchot: Towards a cellular definition of CD8 + T-cell memory: the role of CD4 + T-cell help in CD8 + T-cell responses. In: Current Opinion in Immunology. 16, 2004, p. 259, doi: 10.1016 / j.coi.2004.03.004 .
  7. ↑ Stefanie Hoyer, Sabrina Prommersberger, Isabell A. Pfeiffer, Beatrice Schuler-Thurner, Gerold Schuler, Jan Dörrie, Niels Schaft: Concurrent interaction of DCs with CD4 and CD8 T cells improves secondary CTL expansion: It takes three to tango. In: European Journal of Immunology. 44, 2014, p. 3543, doi: 10.1002 / eji.201444477 .