By Chen Gen The immune system is an exclusive army within each person’s body that belongs to the individual. Different immune cells are always on the line to protect the health of our bodies. Among many immune cells, T cells are an indispensable general, always ready to deal with

text/Chen Gen

The immune system is a personal and exclusive army inside each person's body, and different immune cells are always on the line to protect the health of our bodies. Among many immune cells, T cells are an indispensable general, always ready to deal with various threats from viruses to tumors.

Of course, T cells are not always moving. In fact, T cells sometimes get tired. Recently, a new study published in the journal "science" pointed out that if they are not rested and maintained, T cells may die, making the host more susceptible to pathogens. This is very similar to the classic theory of "eating moderately and living regularly" that is beneficial to health for thousands of years. Perhaps giving T cells a good rest is more important than we think.

T cells that leave the thymus

T cells are the main force in the body's anti-infection and anti-tumor forces, and are also involved in autoimmune diseases . Specifically, T cells have a variety of biological functions, such as directly killing target cells , assisting or inhibiting B cells to produce antibodies, responding to specific antigens and mitogen , and producing cytokines , etc. . It can be said that T cells are heroic warriors in the body that resist disease infections and tumor formation.

However, unlike other immune cells, T cells need to develop in the thymus. T cell development begins with hematopoietic stem cells (derived from fetal bone marrow and liver). The progenitor cells of T cells reach the thymus, which is a primary lymphoid tissue and can secrete several hormones to promote the differentiation and proliferation of T cells . T cells also complete a complex development process in the thymus.

Among them, lymphoid stem cells generated by bone marrow are the precursors of future B cells and T cells. These stem cells will enter the thymus through the action of hormones and differentiate into mature T cells there. Not every mature T cell that proliferates in the thymus can leave the thymus. After some elimination selection in the thymus, only a very small number of T cells can leave the thymus and enter secondary lymphoid tissue.

Take mice as an example. Mice are capable of producing trillions of T cells every day, but only a million can leave the thymus. T cells that can leave the thymus must have the ability to distinguish between their own cells and foreign substances. Cells that do not have these abilities will not only be unable to leave the thymus but will also undergo apoptosis. This process is called positive selection of T cells. In addition, T cells must not be aggressive against their own cells, otherwise T cells will also undergo apoptosis. This choice is a secondary choice.

Only T cells that pass these two selections are eligible to leave the thymus and enter secondary lymphoid tissue to become initial T cells waiting to bind to antigens. There are approximately 300 billion T cells in an adult's body, which fully demonstrates the importance of T cells.

T cells that undergo positive selection and multiple selection can circulate through the lymph and blood systems to peripheral lymphoid organs, such as spleen, lymph nodes, tonsils, , etc. to play a role. Therefore, peripheral lymphoid organs are the battlefield where these T cells carry out actual combat. T cells use the lymph and blood circulation systems to travel in immune organs and various tissues, monitor foreign invaders in real time, and maintain the health of the body.

Most mature T cells express CD4 or CD8 receptor proteins on the cell surface, and therefore can be divided into two main T cell subpopulations, CD4+T cells and CD8+T cells. Once initial T cells discover and recognize foreign antigens during their patrols, they will activate, proliferate, differentiate, and perform defense functions.

Initial T cells are activated by antigen stimulation. According to their active status, T cells can be divided into effector T cells and memory T cells. Among them, memory T cells have long-lasting immune memory characteristics and maintain similar quiescence as initial T cells. Resting state, you can respond quickly and strongly when encountering the enemy again.

Effector T cells are further divided into helper T cells, killer T cells and regulatory T cells. Helper T cells and killer T cells are also the most important T cells for the human body.

Helper T cells participate in almost all adaptive immune responses and play the role of quarterback in the immune system . Helper T cells direct the immune response by secreting chemical messengers (cytokines) that have powerful effects on other immune system cells, such as interleukin 2 (IL-2) and interferon gamma (IFN-γ). process. helper T cells not only help activate B cells to secrete antibodies, activate macrophages to destroy ingested microorganisms, but also help activate cytotoxic T cells to kill infected target cells.

Killer T cells are powerful weapons that can destroy virus-infected cells. By identifying and killing those virus-infected cells, killer T cells solve the problem of "hidden viruses" and can identify virus-infected cells in the body. Or the killer T cells of cancer cells, which are also an important line of defense for the body’s anti-viral and anti-tumor immunity. Because when a virus-infected cell dies, the virus or cancer cells in the cell will also die.

Regulatory T cells are a subpopulation of T cells in the immune system that have significant immunosuppressive and regulatory effects. Regulatory T cells can actively suppress excessive activation of the immune system and are crucial to maintaining immune homeostasis and preventing pathological self-reactions.

Originates from the thymus. Every T cell that has been selected twice is of great significance to the human body. It is precisely because of the defense of T cells that the human immune system can give us sufficient protection.

T cells also get tired sometimes.

Of course, T cells are not always moving. T cells that do not get a rest lead to a weak immune system, and the result of a weak immune system is that the virus can take advantage of it.

In fact, T cells remain in a quiescent state until the pathogen is detected. T cells cannot directly recognize pathogenic microorganisms or viruses. The T cell-mediated immune response begins with the activation of initial T cells by antigen-presenting cells - antigen-presenting cells are activated by ingesting antigens at the site of infection. , the activated antigen-presenting cells will migrate to lymphoid tissue , and at the same time process the ingested antigen and display it on the cell surface to facilitate recognition by initial T cells. initial T cells complete the recognition of antigens by recognizing specific surface molecules of antigen-presenting cells, which is also the induction phase of the immune response .

While recognizing antigens, antigen-presenting cells will further stimulate T cells through specific interactions between their surface molecules and T cell surface molecules, promoting the activation, proliferation and differentiation of T cells. Afterwards, the activated and differentiated T cells further exert effector functions by interacting with other cells or secreting cytokines . In the effector stage, differentiated helper T cells eliminate invading pathogens by secreting cytokines, promoting B cell activation and antibody secretion, activating macrophages, etc.; while activated cytotoxic T cells secrete granzyme Cytokines such as and perforin directly induce apoptosis of infected cells.

In other words, in the absence of antigen exposure, T cells are almost immobile. In other words, the immune system is not "always ready" . Research on this has found that during the resting phase of T cells, if the body does not give T cells enough rest, the T cells will not only weaken their combat effectiveness, but even "die without a fight", making the host more susceptible to pathogens or tumors. Cell attack.

The research results come from a latest study published in "Science" on May 26, that is, the research team led by Yale University famous immunologist Professor Lieping studied immune cells.

Researchers found that a protein called CD8α is present in CD8+ T cells, which plays a key role in CD8+ T cells maintaining a dormant state.

Based on this, the researchers established a mouse model with inducible knockout of CD8α. They found that CD8+ T cells in mice lacking CD8α were unable to enter a dormant state and die, leaving the host susceptible to infection, which is critical for the animal's survival and gene diversity .In other words, CD8α may be the key to keeping these T cells in this dormant state.

In addition, the researchers also discovered another protein called PILRa, which provides a biochemical signal for CD8a. By destroying this pair of proteins, causes both "memory" CD8+ T cells (CD8+ T cells that have been previously exposed to pathogens) and naïve CD8+ T cells (CD8+ T cells that have not been previously exposed to pathogens) to die because they lack The ability to remain still.

That is to say, in the absence of antigen stimulation, the resting state of CD8+ T cells is maintained through specific receptor-ligand (CD8α-PILRα) interactions on the cell surface. This interaction may have Helps desensitize memory CD8+ T cells during antigen-induced activation, preventing them from overactivating when not needed, and helping them return to their normal state after the immune response subsides.

This means that the dormant state is crucial for maintaining the survival of T cells, which directly affects immune system function. You must know that as people age, they tend to lose memory CD8+ T cells and naive CD8+ T cells. Making older adults more susceptible to infection. A research team discovered that after humans reach the age of 40, the immune cells in the body begin to age significantly. New discoveries based on T cells may provide new understanding of improving immune system function.