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T cells are like soldiers who seek and destroy invaders, and support other immune cells for a combined response to threats. T cells are also known as T lymphocytes, with the “T” standing for “thymus” – the organ in which these cells develop and because they mature from thymocytes (hematopoietic progenitor cells present in the thymus) though a few also mature in the tonsils[1].

The different kinds of T Cells

The majority of human T cells are part of the adaptive immune system. T cells have a number of variants which perform differing roles within the immune system.

Effector: These are relatively short-lived activated cells that defend the body during the immune response. The category of effector T cells is a broad one that includes various T cell types, which carry out cell-mediated responses and actively respond to stimulus, such as co-stimulation. This category includes helper, killer, regulatory, and potentially other T cell types, as well as B cells.

Helper: The T helper cells support other white blood cells with immunologic processes, including the maturation of B cells into plasma cells and memory B cells, the activation of cytotoxic T cells and macrophages. These cells are also called CD4+ T cells because they express the CD4 glycoprotein on their surfaces.

Helper T cells become activated by certain antigens on the surface of antigen-presenting cells (APCs), which include macrophages, dendritic cells, langerhans cells, and B cells. T cells detect fragments of protein antigens that have been partly degraded inside the APC. These peptide fragments are carried to the surface of the APC on special molecules called MHC proteins, which then allow the T cells to detect them and become activated.

Once they are activated, they divide quickly and secrete protein signals known as cytokines, which regulate and support the immune response. These cells can differentiate into one of several subtypes (TH1, TH2, TH3, TH17, TH9, or TFH), which secrete different cytokines for different kinds of immune responses. The signalling from the APC determines what subtype a Helper T cell becomes[1].

Cytotoxic T Cell: These cells are also known as CD8+ T cells, since they express the CD8 glycoprotein at their surfaces, but are more commonly called the killer T cells. These cells are designed to seek and destroy pathogens, including viruses and bacterial invaders, as well as tumours. The Killer T cells detect these threats by sensing antigens (a toxin or other foreign substance) when encountering a threat.

Once the T cells have located a threat, such as an influenza virus for example, they have three weapons in their arsenal to use.

The first is the secretion of cytokines, in particular the cytokines TNF-α and IFN-γ, which have antitumour, antiviral, and antimicrobial effects.

The second is the production and release of cytotoxic granules known as granzymes. These granzymes, are also found in natural killer cells, and contain two families of proteins, perforin, and granzymes. Perforin forms a pore in the membrane of the target cell, allowing the granzymes to enter the target cell. The granzymes then cleave the proteins inside the cell, shutting down the production of viral proteins and ultimately resulting in apoptosis (cell death) of the target cell.

The third is using Fas/FasL interactions. Activated killer T cells express FasL on the cell surface, which binds to its receptor, Fas, on the surface of a target cell. The binding causes the Fas molecules on the surface of the target cell to trigger the caspase cascade, which results in apoptosis of the target cell. Importantly, killer T cells also express both molecules, making Fas/FasL interactions a mechanism by which killer T cells can destroy each other – a process called “fratricide” – to remove themselves at the end of an immune response.

Memory: Memory T cells are a type of antigen-specific T cell that remains long after an infection has resolved. When they encounter an antigen associated with a pathogen they encountered in the past, they quickly expand to large numbers of effector T cells capable to destroy the pathogen. This provides the immune system with a “memory” against past infections and allows a faster response to attack. So, for example, if you had an illness such as chickenpox or the mumps as a child, you are much better able to fight off any future occurrences, as your immune “memory” can identify them faster.

Regulatory: These T cells are crucial for the upkeep of immunological tolerance, ensuring there is no immune response to self-antigens and for suppressing excessive immune responses damaging to the host. Their main role is to shut down T cell-mediated immunity towards the end of an immune reaction and to suppress autoreactive T cells that escape the process of negative selection in the thymus.

Regulatory T cells can develop either in the thymus, and are known as thymic Treg cells, or they can also be induced peripherally and are called peripherally derived Treg cells.

Natural killer T cell: Natural killer T cells (NKT cells – different to natural killer cells of the innate immune system) link the adaptive immune system and the innate immune system. Similar to regular T cells which recognise certain antigens, these cells detect a different set of antigens (glycolipid antigens); once activated, they can function in a twin capacity like T helper and T killer combined into one.

This means NKTs can release cytokines to support the active immune response and use the cytotoxic weapons available to regular T cells.

Others: There are some other types of T cells, such as mucosal associated invariant T cells and gamma delta T cells (part of the innate immune system), but these represent very small numbers and are beyond the scope of this general introduction.

Conclusion

The body has evolved numerous defensive systems to prevent viral invasion and microbial attack; the T cells are the soldiers of the immune system, hunting down and destroying invaders. Some researchers are working on producing T cells that can more effectively target cancer and other hard-to-treat diseases that can evade the normal immune system. 

Literature

[1] McClory, S., Hughes, T., Freud, A. G., Briercheck, E. L., Martin, C., Trimboli, A. J., … & Caligiuri, M. A. (2012). Evidence for a stepwise program of extrathymic T cell development within the human tonsil. The Journal of clinical investigation, 122(4), 1403-1415.

[2] Gutcher, I., & Becher, B. (2007). APC-derived cytokines and T cell polarization in autoimmune inflammation. The Journal of clinical investigation, 117(5), 1119-1127.

 

 

CategoryBlog, Education
About the author
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Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).
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