T-cell lymphocyte

BACKGROUND

T-cells, also called thymus cells or thymocytes, are a type of white blood cell called lymphocytes. They help fight against disease and infection.

T-cells cells play a vital role in cell-mediated immunity. Once activated, T-cells secrete chemical messengers called cytokines, which stimulate immune system cells to engulf foreign substances (such as bacteria, viruses, fungi, and allergens) that enter the body.

T-cells are continually produced in the bone marrow. The immature T-cells then migrate through the bloodstream and mature in the thymus gland, which is located in the upper chest.

These cells can be distinguished from other types of lymphocytes (B-cells) by the receptor on the outside of their cells called the T-cell receptor (TCR). This receptor allows T-cells to identify specific antigens (foreign substances) that enter the body.

There are several types of T-cells, including cytotoxic T-cells, Helper T-cells, memory T-cells, regulatory T-cells, natural killer (NK) T-cells, and Gamma/delta (Yd) T-cells. Each type of T-cell has a distinct function.

DEVELOPMENT

T-cells are continually produced in the bone marrow. T-cells in the bone marrow are considered immature because they are not fully developed. During this stage, the T-cells do not have receptors on their surfaces yet because they do not express CD4 or CD8 glycoproteins (carbohydrate and protein molecules located on the surface of T-cells). Therefore, they are considered double-negative cells (Cd4- Cd8-).

The cells then enter the bloodstream and travel to the thymus gland, where they develop into mature T-cells.

The T-cells develop receptors on their outer surfaces. This means they express both CD4 and CD8 glycoproteins on their surfaces. Because they express both glycoproteins, these cells are called double-positive T-cells (CD4+ Cd8+).

These cells then move to the outer layer of the thymus gland. Here, the T-cells are presented with self-antigens (antigens that are derived from the host), which are combined with what is called either a class I or class II major histocompatibility complex (MHC) molecule from the surfaces of cells that line the internal and external surfaces of the body. The MHC molecules help T-cells detect host cells that have been invaded by infectious organisms. These molecules present parts of the foreign invader's proteins on the surface of the host cell for the T-cell to identify. This is called the MHC peptide. Once a T-cell recognizes the MHC peptide, it binds to it.

Only the T-cells that are able to successfully bind to the MHC peptide will survive and continue to mature. The other 98% that are unable to bind to the MHC peptide die in a process called apoptosis (programmed cell death). Other immune cells called macrophages engulf the dead T-cells. This process is called positive selection.

The T-cells that survived will mature into single-positive cells. This means that they either have CD4 or CD8 on their cell surfaces. Whether the cell has CD4 or CD8 depends on the molecule for which it was positively selected. T-cells that were positively selected on MHC class I molecules will become CD8 cells, while T-cells that were positively selected on MHC class II cells will become CD4 cells.

Then, the mature T-cells move towards the central portion of the thymus gland, called the thymic medulla. Here, the T-cells are presented with another self-antigen that is combined with MHC molecules on antigen-presenting cells (APCs) like B-cells, dendritic cells, and macrophages.

The thymocytes that interact too strongly with the antigen receive an apoptosis signal from the APC, which stimulates their death. A minority of the surviving cells become regulatory T-cells, while the remaining are released into the bloodstream as mature native T-cells. This process, which is called negative selection, is important because it ensures that the T-cells are able to recognize body cells. This prevents the development of autoimmune disorders. Autoimmunity occurs when the body's immune cells mistakenly destroy body cells because they are perceived as foreign invaders.

Once the T-cells have been successfully activated, they become helper T-cells, also called CD4 T-cells or effector cells. These cells divide rapidly and secrete proteins called cytokines, which trigger immune cells to engulf the antigen. It also stimulates cellular division (multiplication) of both T-cells and antibody-producing B-cells.

ACTIVATION

In order for the T-cell to become fully activated, the cell must receive two signals. The first occurs when the T-cell identifies a foreign substance, and the second occurs after it binds to the invader.

During an immune response, antigen-presenting cells (APCs) absorb foreign substances (like bacteria and viruses) that enter the body. The APC attaches parts of the antigen's (foreign substance) proteins to a major histocompatibility complex (MHC) class II molecule. This complex, which is called a MHC peptide, is then transported to the outside of the cell membrane, where specific T-cells can identify it.

The first signal occurs when the T-cell then binds its receptor to the MHC peptide on the APC. If the T-cell receptor is activated when it encounters the MHC peptide, but there is no binding between the two molecules, anergy (lack of immune response) will result.

The second signal occurs when the APC releases cytokines (chemical messengers) that signal the T-cell to destroy the antigen. This second signal is necessary to ensure that the T-cell is not mistaking a body cell for a foreign invader. If the second signal is not received, the T-cell will become anergic (unable to launch an immune response).

Once the T-cells have been successfully activated, they become helper T-cells, also called CD4 T-cells or effector cells. These cells divide rapidly and secrete proteins called cytokines, which trigger immune cells to engulf the antigen. It also stimulates the cellular division (multiplication) of both T-cells and antibody-producing B-cells.

TYPES OF T-CELLS

Cytotoxic T-cells: Cytotoxic T-cells, also called CD8 T-cells, destroy cells that are infected with viruses and tumors. Their T-cell receptors, located on their cell surfaces, are made up of CD8 glycoproteins. They contain pouches, called granules, which are filled with chemicals that kill infected cells on contact.

These cells are also involved in transplant rejection. The cytotoxic T-cells attack the donated organ because it is perceived as an infected body cell.

Helper T-cells: Activated T-cells become helper T-cells, also called CD4 T-cells, or effector cells. These cells divide rapidly and secrete proteins called cytokines, which trigger the cellular division (multiplication) of both T-cells and antibody-producing B-cells.

The CD-4 cells are targeted in patients who have HIV (human immunodeficiency virus). The virus uses the helper T-cell's receptor to gain entry and infect the cell. As the virus continues to infect and destroy these cells, patients begin to experience symptoms of HIV infection, which eventually leads to AIDS (acquired immune deficiency syndrome).

Memory T-cells: There are two types of memory cells - central memory T-cells and effector memory T-cells. Their T-cell receptors are either made up of CD4 or CD8 glycoproteins. Memory T-cells have already encountered antigens (like viruses or bacteria) in the body. Therefore, low levels of the antigen are able to activate memory T-cells and they are able to respond quickly to these antigens in the future. Memory T-cells can survive for many years (up to a lifetime).

Regulatory T-cells: Regulatory T-cells, formerly called suppressor T-cells, stop the T-cells from becoming activated towards the end of an immune reaction. They also suppress dysfunctional T-cells that mistakenly attack body cells because they are identified as foreign invaders. If the regulatory T-cells do not function properly, it can lead to autoimmune diseases (like lupus), which occur when the immune system attacks the body's cell and tissues.

There are two major types of T-cells: naturally occurring T-reg cells and adaptive T-reg cells. The naturally occurring T-reg cells are continually produced in the thymus gland, while the adaptive T-cells are produced during an immune response. Naturally occurring T-reg cells can be distinguished from other T-cells because they have an internal molecule called FoxP3. Patients who are born with a mutated (defective) FoxP3 gene cannot produce these cells. Deficiencies in naturally occurring T-reg cells can lead to a fatal autoimmune disease called IPEX (immune dysregulation, polyendocrinopathy, enteropathy X-linked) syndrome. Patients with IPEX syndrome typically have concurrent autoimmune disorders, and often suffer from symptoms such as diarrhea, eczema (dry, flaky skin), and hormonal imbalances (that often lead to diabetes).

Natural killer (NK) T-cells: Natural killer (NK) T-cells recognize and destroy body cells that have become infected with viruses or cancer. They have pouches, called granules, which are filled with chemicals that destroy infected cells on contact.

Unlike cytotoxic cells, the NK T-cells do not need to recognize the specific MHC peptide on the surface of other immune cells to become activated. Instead, they attack cells that do not have external molecules that label them as body cells.

Gamma/delta (Yd) T-cells: Gamma/delta (Yd) T-cells have a distinct T-cell receptor (TCR) on the surfaces of their cells. This receptor is made up of one gamma (y)-chain and one delta (d)-chain. These T-cells make up five percent of all T-cells in the body. They are more prevalent in the lining of the gut.

It remains unknown how these T-cells become activated. However, unlike most other T-cells, gamma/delta T-cells are able to identify whole antigens rather than MHC peptides (antigens that have been processed by other immune cells).

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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