What Are T Cells? A Summary of T Lymphocytes

In this article, we will be taking a look at T cells and their role in the adaptive immune system.

T cells’ definition

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), although a few also mature in the tonsils [1].

T cells’ function

The majority of human T cells are part of the adaptive immune system. T cells have a number of variants that perform differing functions within the immune system. In the next section, we will describe these T cell variants and their functions.

Effector T cells

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 along with B cells.

Helper T cells

The helper T cells support other white blood cells with immunologic processes, including the maturation of B cells into plasma cells and memory B cells along with 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, and TFH), which secrete different cytokines for different kinds of immune responses. The signaling from the APC determines what subtype a helper T cell becomes [2].

Cytotoxic T cells

These cells are also known as CD8+T cells, since they express the CD8 glycoprotein at their surfaces, but they are more commonly called killer T cells. These cells are designed to seek and destroy pathogens, including viruses and bacterial invaders, and tumors. Killer T cells detect these threats by sensing antigens (toxins or other foreign substances) 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 antitumor, antiviral, and antimicrobial effects.

The second is the production and release of cytotoxic granules known as granzymes, which natural killer cells secrete along with the protein perforin. 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 (cellular death).

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 also 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 T cells

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 that 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. 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 T cells

These T cells are crucial for the upkeep of immunological tolerance, ensuring that 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, making them thymic Treg cells, or they can also be induced peripherally, making them peripherally derived Treg cells.

Natural killer T cells

Natural killer T cells (NKT cells) are different from natural killer cells of the innate immune system, as they link the adaptive immune system and the innate immune system. Similar to regular T cells, which recognize certain antigens, these cells detect a different set of antigens (glycolipid antigens); once activated, they can function in a double capacity, as if they were T helper and T killer cells combined into one.

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

Other types of T cells

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 are only present in 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.