Immune Guard T cells are also tired sometimes

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The immune system is an exclusive army within each person's body that belongs to the individual, and different immune cells are always charging for the defense of our body's health. Among the many immune cells, T cells are an indispensable member, always ready to deal with various threats from viruses to tumors.

Of course, T cells are not perpetually moving. In fact, T cells also get tired sometimes. A new study published in the journal Science shows that if not rested and maintained, T cells can die, making the host more susceptible to pathogens. This is very similar to the classic theory that "a healthy diet and a regular life" have been healthy for thousands of years. Perhaps, giving T cells a good rest is more important than we thought.

T cells leaving the thymus

T cells are the main force of the body's anti-infection, anti-tumor, and also participate 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 mitogens, and producing cytokines. It can be said that T cells are the heroic warriors in the body to resist disease infection and tumor formation.

Unlike other immune cells, however, T cells need to develop in the thymus. T cell development begins with hematopoietic stem cells (derived from fetal bone marrow and liver), and T cell progenitor cells reach the thymus, which is a primary lymphoid tissue that secretes several hormones to promote T cell differentiation and proliferation. T cells also complete complex developmental processes in the thymus.

Among them, lymphoid stem cells generated from bone marrow are the precursors of future B cells and T cells. These stem cells enter the thymus through the action of hormones and differentiate into mature T cells there. Not all T cells that proliferate and mature in the thymus can leave the thymus. After the thymus undergoes a selection process, only a very small number of T cells can leave the thymus and enter the secondary lymphoid tissue.

In the case of mice, mice are capable of producing trillions of trillions of T cells per day, but only a million can leave the thymus. T cells that can leave the thymus must have the ability to identify their own cells and foreign bodies. Cells that do not have these abilities not only cannot leave the thymus, but also go to apoptosis. This process is called positive selection of T cells. In addition, T cells must not be aggressive to their own cells, otherwise T cells will also go to apoptosis, which is a secondary selection.

Only T cells that have passed these two selections are eligible to leave the thymus and enter the secondary lymphoid tissue to become naive T cells waiting to bind to the antigen . There are about 300 billion T cells in the body of an adult, and this number has fully demonstrated the importance of T cells.

T cells that have been positively selected and reselected can circulate through the lymphatic and blood systems to peripheral lymphoid organs, such as the spleen, lymph nodes, tonsils, and the like. Therefore, the peripheral lymphoid organs are the actual combat positions of these T cells. T cells travel in immune organs and various tissues with the help of the lymphatic and blood circulatory system, 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, so they can be divided into two major T cell subsets, CD4+ T cells and CD8+ T cells. Once the naive T cells discover and recognize foreign antigens during the patrol process, they will activate, proliferate, differentiate, and perform defense functions.

Naive T cells are activated by antigen stimulation. According to the active state, T cells can be divided into effector T cells and memory T cells. Memory T cells have long-term immune memory characteristics and maintain a resting state similar to that of initial T cells. Status, which can respond quickly and strongly when encountering an 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 in the human body.

Helper T cells are involved in almost all adaptive immune responses and act as quarterbacks in the ranks of the immune system . Helper T cells direct the process of 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). 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 "hidden virus" and can recognize the body's virus-infected cells or cells. Killer T cells of cancer cells are also an important defense line of the body's anti-virus and anti-tumor immunity. Because when a virus-infected cell dies, the virus or cancer cells inside the cell die with it.

Regulatory T cells are a subset of T cells with significant immunosuppressive and regulatory effects in the immune system. Regulatory T cells can actively suppress the overactivation of the immune system and are essential for maintaining immune homeostasis and preventing pathological self-reactions.

Originating 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 protection of T cells that the human immune system can give us sufficient protection.

T cells get tired too

Of course, T cells are not perpetually moving either. The T cells that do not get rest bring the weakening of the immune system, and the result of the weakening of the immune system is that the virus can take advantage of it.

In fact, T cells remain in a quiescent state until a pathogen is detected. T cells also cannot directly recognize pathogenic microorganisms or viruses. The immune response mediated by T cells begins with the activation of naïve T cells by antigen-presenting cells. Antigen-presenting cells migrate to the lymphoid tissue and simultaneously process the ingested antigen and display it on the cell surface for recognition by naive T cells. Naive T cells complete antigen recognition by recognizing antigen-presenting cell-specific surface molecules, which is also the induction phase of the immune response .

While recognizing antigens, antigen-presenting cells will further stimulate T cells through the specific interaction of their surface molecules with T cell surface molecules, promoting T cell activation, proliferation and differentiation. Thereafter, activated and differentiated T cells further perform 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, and activating macrophages; while activated cytotoxic T cells secrete granzymes and Cytokines such as perforin directly induce apoptosis in infected cells.

That is, 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 in the resting phase of T cells, if the body does not give T cells enough rest, T cells will not only be weakened, but even "die without a fight", making the host more vulnerable to pathogens or tumors. Cell attack.

The findings come from a new study published in Science on May 26, that is, a research team led by Professor Chen Ping, a well-known immunologist at Yale University, conducted research on immune cells.

The researchers found that a protein called CD8α, which is present in CD8+ T cells, plays a key role in how CD8+ T cells maintain a dormant state.

Based on this, the researchers established a mouse model of 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 vulnerable to infection, which is critical for animal survival and genetic diversity. In other words, CD8α may be the key to keeping these T cells in this dormant state.

In addition, the researchers identified another protein called PILRa, which provides a biochemical signal to CD8a. By disrupting this pair of proteins, both "memory" CD8+ T cells (CD8+ T cells that have previously been exposed to the pathogen) and naive CD8+ T cells (CD8+ T cells that have not previously been exposed to the pathogen) die because they lack retention The ability to stand still.

That is, in the absence of antigenic stimulation, the quiescent state of CD8+ T cells is maintained through specific receptor-ligand (CD8α-PILRα) interactions on the cell surface that may contribute to It desensitizes memory CD8+ T cells during antigen-induced activation, does not overactivate them when they are not needed, and helps them revert to a normal state after the immune response has subsided.

This means that the dormant state is crucial to maintaining the survival of T cells, which directly affects immune system function, knowing that as people age, people tend to lose memory CD8+ T cells and naive CD8+ T cells, making Older people are more susceptible to infection. A research team has found that after the age of 40, the immune cells in the body begin to age significantly. New findings based on T cells may provide new insights into improving immune system function.