T Lymphocytes: Structure, Functions, Types, Maturation

The T lymphocytes or T cells are immune system cells the active in the cellular immune system response and contributing to the activation of antibody – producing cells in the humoral immune response system.

These, like B cells and natural killer (NK) cells, are blood cells (leukocytes) that originate in the bone marrow and together with B cells constitute between 20 and 40% of the total leukocytes in the blood.

Representative diagram of the hematopoietic process in humans that gives rise to the lymphoid lineage (Source: Jmarchn [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)] via Wikimedia Commons)

Its name derives from the place where they mature before exercising their functions (the thymus ) and the term was coined by Roitt in 1969.

There are different types of T lymphocytes and these differ from each other both by the expression of certain surface markers and by the function they exert. Thus, two main groups have been described which are known as “helper” T lymphocytes and “cytotoxic” T lymphocytes.

Helper T lymphocytes participate in the activation of antibody-secreting B lymphocytes, while cytotoxic T lymphocytes directly mediate the elimination of cells infected by viruses, parasites, and other intracellular microorganisms.

These cells are extremely important, since they perform fundamental functions in various immunological aspects and are essential for the adaptive defense system.

Article index

  • one

    Structure of T lymphocytes

  • two

    Features

  • 3

    Types of T lymphocytes

    • 3.1

      Helper T lymphocytes or “helpers”

    • 3.2

      Regulatory T lymphocytes (Tregs)

    • 3.3

      Cytotoxic or cytolytic T lymphocytes

    • 3.4

      Memory T lymphocytes

  • 4

    Maturation

  • 5

    Activation

    • 5.1

      Activation of helper T cells

    • 5.2

      Activation of cytotoxic T cells

    • 5.3

      Signal transduction

  • 6

    References

Structure of T lymphocytes

Super-resolution image of a cluster of cytotoxic T cells surrounding a cancer cell. Source: The National Institutes of Health / Public domain

T lymphocytes are small cells, with a size comparable to that of an average bacterium: between 8 and 10 microns in diameter. They have a characteristic spherical shape and their cytosol is occupied mainly by a large nucleus surrounded by few organelles.

All lymphocytes arise from precursors from “primary” or “generative” lymphoid organs. In the case of T lymphocytes, these are produced in the bone marrow and then migrate to the thymus for maturation (the thymus is a glandular organ located behind the chest bone).

Once mature, they are released into the bloodstream, but they perform their functions in other places known as “secondary lymphoid organs.”

T lymphocytes, as is true for B lymphocytes, are blood cells capable of producing antibodies against specific antigens, with the difference that they cannot release them into the circulation.

Antibodies expressed by T cells are proteins bound to the plasma membrane, with antigen recognition sites “facing” towards the extracellular environment. These antibodies are known as “T cell antigen receptors” or TCR ( T Cell Receptor ).

TCRs are transmembrane heterodimers composed of two polypeptide chains linked together by disulfide bridges. Each T cell presents a TCR with a unique specificity.

Features

3D rendering of a T cell. Source: Blausen Medical / CC BY (https://creativecommons.org/licenses/by/3.0)

T lymphocytes play a fundamental role in the development of the adaptive or specific immune response system. They are multifunctional cells, as they serve different purposes in the “battle” against invading and potentially pathogenic antigens.

Some T cells help in the production of antibodies mediated by B lymphocytes; others are capable of interacting with blood cells of the myeloid lineage to help them more efficiently destroy pathogens, while others function directly in the elimination of virus-infected cells or tumor cells.

Another of their functions is as regulatory cells by conferring immunological “tolerance” to the organisms where they act or by establishing some “limits” to the amplitude of the responses that are triggered.

Types of T lymphocytes

Scanning electron micrograph of a red blood cell (left), a platelet (center), and a T lymphocyte (right). Source: Electron Microscopy Facility at The National Cancer Institute at Frederick (NCI-Frederick) / Public domain

The different types of lymphocytes are distinguished from each other by the expression of specific membrane receptors that are recognized experimentally by artificial monoclonal antibodies.

These receptors recognized by the aforementioned antibodies belong to what is known as a “group of differentiation” or CD ( Cluster of Differentiation ).

The designation of CD refers to a cell phenotype and, although not necessarily specific for a cell type or an entire cell lineage, it has been useful for the characterization of lymphocytes.

Functionally, some authors consider that T lymphocytes can be classified as helper T lymphocytes and cytotoxic or cytolytic T lymphocytes. Both types of cells express similar T-lymphocyte receptors (TCRs), but differ in the expression of CD proteins.

Other authors, however, introduce an additional category defined as “memory T cells” or “memory T lymphocytes”.

Helper T lymphocytes or ” helpers”

Helper T cells do not have the primary function of directly “attacking” or “recognizing” any antigenic molecule, instead, they are specialized in the secretion of cytokines, which promote or enhance the functions of other cells such as B lymphocytes.

These cells express CD4 group proteins on their surface, which function as coreceptors for the proteins of the class II major histocompatibility complex. In other words, these proteins recognize antigens presented in the context of MHC class II.

In the literature, names can be obtained for different types of helper T cells, which are distinguished from each other by the secretion of different types of cytokines and the response to certain interleukins.

Thus, type 1 helper T lymphocytes (TH1) that secrete the cytokine IFN-γ (useful for macrophage activation and pathogen elimination) have been defined; type 2 helper T cells (TH2) that secrete large amounts of IL-4, IL-5, and IL-13 (these TH2 promote antibody production).

There are also other helper lymphocytes known as “follicular helper T lymphocytes” (THF) which, as their name implies, are present in lymphoid follicles and assist in the activation of B cells and the stimulation of antibody production.

These THFs also secrete a wide variety of different cytokines, participating, at the same time, in the stimulation of the production of antibodies associated with the immune response mediated by TH1 and TH2 cells.

Type 9, type 17, and type 22 helper T cells have also been described, controlling very specific aspects of certain immune responses.

Regulatory T lymphocytes (Tregs)

There is also another set of T cells that express CD4 receptors that are known as regulatory CD4 T lymphocytes or “Tregs”. These lymphocytes produce a transcription factor called FoxP3 and express another CD marker on their surface called CD25.

Regulatory T cell functions (Source: Gwilz [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)] via Wikimedia Commons)

Its regulatory mechanisms consist of intercellular contacts, expression of surface molecules, increased response to growth factors, and altered production of regulatory cytokines such as TGF-β1 and IL-10.

Cytotoxic or cytolytic T lymphocytes

Cytotoxic T cells, on the other hand, are in charge of attacking and destroying invasive or foreign cells, thanks to their ability to bind to these and release special granules loaded with different types of cytotoxic proteins.

Perforins and granzymes contained in the cytotoxic granules of cytolytic T cells have the ability to open pores in the plasma membrane and degrade proteins, respectively, resulting in lysis of the cells they attack.

Multiplication and action of cytotoxic T cells and their respective memory T cells (Source: OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)] via Wikimedia Commons)

This type of T lymphocyte is especially responsible for the degradation of cells that have been infected by viruses, bacteria or intracellular parasites, as well as cancer or tumor cells.

Cytotoxic T lymphocytes are recognized by the membrane expression of CD8-like proteins, which are proteins capable of recognizing and binding antigens that are presented to it in the context of other membrane proteins: those of the major class I histocompatibility complex.

Memory T lymphocytes

As already mentioned, “naive”, “innocent” or ” naive ” T lymphocytes differentiate once they come into contact with an antigen. This differentiation not only gives rise to CD4 and CD8 T cells, but also to another class of T cells known as memory cells .

These cells, as is true for memory B lymphocytes, have much longer life spans and their cell populations expand and differentiate into effector T cells, such as CD4 and CD8, when they come into contact with it again. antigen.

Memory cells can have CD4 or CD8 markers and their main function is to provide “molecular memory” to the immune system against “known” pathogens.

Maturation

T lymphocytes are rigorously selected and mature in the thymus. During the maturation process, these cells acquire the ability to express an antigen receptor protein on their membrane: the T cell receptor.

The hematopoietic precursor cells of T lymphocytes migrate to the thymus in very early stages of development and maturation consists, essentially, in the rearrangement of the genes that code for TCR receptors and other membrane markers.

The precursors of T cells, when they reach the thymus, are known as “thymocytes”, which are those that multiply and differentiate into the different subpopulations of mature T cells.

In the thymus there is both a positive selection of cells that recognize foreign antigens, and a negative selection, which eliminates cells that recognize self-molecules.

Maturation occurs initially in the outer thymus cortex, where cells proliferate at a very low rate.

Activation

T lymphocytes, while not in contact with an antigen, remain in the G0 phase of the cell cycle, in a kind of senescence.

The term activation refers to all the events that take place during the “commitment” of antigenic receptors in the membrane of these cells, which merits the participation of helper cells, which in some texts are defined as antigen presenting cells or APCs. (from the English Antigen Presenting Cells ).

APCs contain membrane molecules on their surface that “show” antigens to T cells. These are known as ” Major Histocompatibility Complex ” or MHC ( Major Histocompatibility Complex ) molecules .

Activation process of a T lymphocyte. Antigenic receptors and antigens presented are represented in the context of class II major histocompatibility complex (MHC) proteins (Source: Cecilia Tejero García [CC BY-SA 4.0 (https: //creativecommons.org/licenses/by-sa/4.0)] via Wikimedia Commons)

In the course of the activation process, the lymphocytes increase in size and change from the original spherical shape to a shape similar to a hand mirror, and during this phase the lymphocytes are known as lymphoblasts.

Lymphoblasts, unlike inactive lymphocytes, have the ability to proliferate mitotically, generating other cells capable of differentiating.

Activation of helper T cells

TH cells can only be activated when APC cells “present” them a foreign antigen with the help of MHC class II molecules. The first step in this activation pathway consists of recognition of the presented antigen by the TCR receptor.

Subsequently, the CD4 helper cell interacts with a region of the MHC II molecule, so that a complex is formed between the TCR protein, the antigen and the MHC II molecule, which ensures the recognition of both the antigen and the molecules presented by the APC.

Then, both the T cell and the antigen-presenting cell secrete regulatory cytokines that help activate the CD4 helper T cell that is being activated. Once activated, this lymphocyte multiplies and produces new ” naive ” CD4 T lymphocytes that differentiate into the other types of memory or effector lymphocytes.

Activation of cytotoxic T cells

The sequence of steps that takes place during the activation of CD8 lymphocytes is very similar to that of helper T cells. However, the MHC molecules involved belong to class I.

Once antigens and receptors are recognized, the APC cells involved in this process and the activating cytotoxic T lymphocytes secrete cytokines that activate clonal proliferation and differentiation of lymphocytes.

As with CD4 T cells, CD8 T cells can differentiate into effector cells or memory cells, in which case they act as cytotoxic or molecular memory cells, respectively.

Activation of CD8 T lymphocytes is achieved thanks to the participation of other helper T cells, specifically type 1 cells.

Signal transduction

The activation of lymphocytes involves the transduction of signals from the extracellular environment into the cytosolic space and the nucleus. These signals are perceived by antigenic receptors present on the plasma membrane and translated by internal signaling pathways.

The ultimate goal of receiving these signals is to activate the transcription of specific genes, which code for specific surface proteins.

It is important to mention that lymphocytes that are activated and do not differentiate (mature) are eliminated from the body by apoptosis or programmed cell death.

References

  1. Abbas, A., Murphy, K., & Sher, A. (1996). Functional diversity of helper T lymphocytes. Nature , 383 , 787-793.
  2. Actor, JK (2014). Introductory Immunology Basic Concepts for Interdisciplinary Applications . London: Academic Press.
  3. Cavanagh, M. (nd). T-cell activation. British Society for Immunology .
  4. Heath, W. (1998). T Lymphocytes. In Encyclopedia of Immunology (pp. 2341-2343). Elsevier.
  5. Kindt, T., Goldsby, R., & Osborne, B. (2007). Kuby’s Immunology (6th ed.). Mexico DF: McGraw-Hill Interamericana of Spain.
  6. Martin, S. (2014). T Lymphocytes as Tools in Diagnostics and Immunotoxicology . T lymphocytes as tools in diagnostic and immunotoxicology (Vol. 104). Springer.
  7. Pinchuk, G. (2002). Schaum’s Outline of Theory and Problems of Immunology . The McGraw-Hill Companies.
  8. Reinherz, E., Haynes, B., Nadles, L., & Bernstein, I. (1986). Leukocyte Typing II . Human T Lymphocytes (Vol. 1). Springer.
  9. Smith-Garvin, JE, Koretzky, G. a, & Jordan, MS (2009). T Cell Activation. Annu. Rev. Immunol. , 27 , 591-619.

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