Thymus is located behind the sternum, close to the heart, gray-red, flat oval, divided into left and right lobes, composed of lymphoid tissue. Hair is well filled before puberty, but gradually degenerates after puberty and is replaced by adipose tissue.

Thymus is a hematopoietic organ, which can produce lymphocytes and transport them to lymph nodes and spleen. These lymphocytes play an important role in the cellular immunity of the body.

Growth hormone and thyroxine can stimulate thymus growth, while sex hormones can promote thymus degeneration.

Thymosin is a kind of protein and polypeptide hormone produced by thymus gland, which can stimulate T lymphocytes to mature, balance and regulate immune function, and is a hormone closely related to cellular immunity. When people reach adulthood, the thymus gradually shrinks, and the secretion of thymosin drops sharply or is absent. At this time, it is necessary to supplement thymosin to improve the body with weakened immune function.

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thymus

1. The structure of thymus The thymus is composed of epithelium of branchial groove ectoderm and pharyngeal pouch endoderm in early embryos, so its early primordia are epithelial tissues containing ectoderm and endoderm; Lymphatic stem cells gradually transform into a special lymphoid tissue after transplantation. Children's thymus is a thin pink soft tissue, divided into two pieces, with a thin connective tissue capsule on the surface. The connective tissue of the capsule extends into the thymus parenchyma to form interlobular septa, which divides the thymus into many incomplete lobules. Each lobule is divided into cortex and medulla. Thymus cells in the cortex are dense, so the color is dark. The medulla contains more epithelial cells, so it is lighter in color. The lobular medulla is usually interconnected in the deep thymus (Figure 9-6).

Figure 9-6 Thymus of Children

(1) cortex: The cortex is supported by epithelial cells, with a large number of thymocytes and a small number of macrophages in the gap (Figures 9-7 and 9-8).

Figure 9-7 Distribution Pattern of Cells in Thymus

Fig. 9-8 Electron microscopic image of rat thymus cortex ×7800

(Photo courtesy of Professor Yin Xin and Professor Zhu Xiuxiong from Bethune Medical University)

Thymic epithelial cells: There are two kinds of epithelial cells in cortex: subcapsular epithelial cells and stellate epithelial cells. One side of the subepithelial cells adjacent to connective tissue is a complete flat epithelium with basement membrane, and there are many desmosomes connections between adjacent cells, and there are some protrusions on the other side of the cells. Mammalian cells are rich in cytoplasm, and the cytoplasm contains some endocytotic thymocytes (Figure 9-7), which are similar to the mammary gland cells in the isolated thymocytes. The feeder cell is a large round or oval cell, and its cytoplasm contains several or even dozens of thymocytes, some of which undergo mitosis. They are precursors of Th cells. Subcapsular epithelial cells can secrete thymosin and thymosin. Astrocytes, commonly known as epithelial reticular cells, are multi-branched processes, and the processes are interconnected by desmosomes to form a network. The cell surface markers are different from those of subcapsular epithelial cells, but the same as those of thymic corpuscle epithelial cells. There are many MHC antigens on the surface. This cell does not secrete hormones, and its plasma membrane is close to thymocytes, which can induce the development and differentiation of thymocytes.

Thymic cells: precursors of T cells, concentrated in the cortex, accounting for 85% ~ 90% of the total number of thymic cortical cells. After migrating to thymus, lymphocytes first developed into large early thymocytes (about 3%). After proliferation, they become smaller normal thymocytes, which are characterized by the appearance of T cell antigen receptor (TCR) and the gradual expression of CD4 and CD8 antigens. These cells account for about 75% of the total number of thymocytes, and they have no ability to respond to antigens. Ordinary thymocytes are in the selection stage. All thymocytes (about 95%) that can bind to the body's own antigen or are incompatible with its own MHC antigen will be inactivated or eliminated, and a few selected cells will continue to differentiate, thus establishing a lymphocyte TCR library that meets the needs of the mechanism. One of CD4 and CD8 cells in the further mature normal thymocytes was enhanced, while the other was weakened or disappeared. Results CD4+ cells accounted for about 2/3 and CD8+ cells accounted for 1/3.

(2) Medulla: The medulla contains a large number of thymic epithelial cells and some mature thymocytes, finger cells and macrophages. There are two types of epithelial cells (Figure 9-7): ① Medullary epithelial cells are spherical or polygonal, with large cell bodies, desmosomes between them, and a small number of thymocytes in the gaps. Medullary epithelial cells are the main cells secreting thymosin. ② Thymus corpuscle epithelial cells constitute thymus corpuscle. Thymus corpuscles with a diameter of 30 ~ 150μ m are scattered in medulla and surrounded by concentric circles of epithelial cells, which is an important feature of thymus structure. The epithelial cells around the small cells are naive, with obvious nuclei and divisible cells; The epithelial cells near the center of corpuscle are mature, the cytoplasm contains more keratin, and the nucleus gradually degenerates. The epithelial cells in the center of the corpuscle were completely keratinized, stained with eosinophils, and some cells were broken, homogeneous and transparent. Macrophages or eosinophils are also common in the center. The epithelial cells of thymic corpuscles do not secrete hormones, and their functions are unknown, but the thymus lacking thymic corpuscles cannot cultivate T cells. Although the number of thymocytes in medulla is small, they are all mature and have the ability of immune response. There are also a few scattered staggered cells and macrophages in the medulla, and Th cells often gather near the staggered cells. Macrophages are also involved in the formation of microenvironment in thymus, and their secretions can promote the differentiation of thymocytes.

(3) Blood supply of thymus and blood-thymus barrier: Several arterioles pass through the capsule around thymus and enter interlobular septum, forming arterioles at the junction of cortex and medulla, and issuing many capillaries distributed in cortex. These capillaries join the postcapillary venules at the junction of cortex and medulla, and some capillaries are highly endothelialized, which is the main channel for lymphocytes in thymus to enter and exit blood flow. The capillaries of medulla are usually porous, flow into venules, and flow out of thymus through interlobular septa and capsule. According to statistics, the number of lymphocytes in thymus venous blood of rats is about 65438 0.5 times that of arterial blood.

Experiments show that macromolecules in blood are not easy to enter the thymus cortex, indicating that capillaries and their surrounding structures in the cortex have barrier function, which is called blood-thymus barrier (Figure 9-9). The blood-thymus barrier consists of the following layers: ① continuous capillaries, with tight connections between endothelial cells; ② Endothelial basement membrane; ③ Perivascular space containing macrophages; ④ Epithelial basement membrane; ⑤ Continuous epithelial cell layer.

Figure 9-9 Structure Model of Blood Thymus Barrier

Recently, it has been found that the capillaries in the thymus capsule are porous, and various autoantigen molecules contained in blood can easily seep through them and enter the thymus cortex near the capsule. These small amounts of autoantigens can bind to the corresponding antigen receptors of immature ordinary thymocytes, which leads to the inactivation or elimination of these cells, thus making some T cells produced by thymus immune tolerance or no response to autoantigens. In addition; The perivascular space of medullary blood vessels is large, which contains a variety of cell components, such as T cells, B cells, plasma cells, mast cells, eosinophils, fibroblasts, fat cells and so on. The larger perivascular space may also contain lymphatic capillaries and more lymphocytes, which may be another way for thymus to export lymphocytes.

2. Function of Thymus Thymus is an important organ for cultivating and screening T cells. Thymosin and thymosin secreted by thymic epithelial cells can promote the differentiation of thymocytes, and macrophages and finger cells are also involved in the formation of thymic microenvironment. All kinds of virgin T cells cultured in thymus are transported to the surrounding lymphatic organs and tissues through blood flow.

Thymus has obvious aging changes. The thymus in infancy is very large and weighs about 27g. After that, it gradually degenerated, the cortex gradually became thinner, the number of thymocytes gradually decreased, the boundary between cortex and medulla gradually became inconspicuous, thymus corpuscles increased, and fat cells gradually increased. After the age of 85, there are few thymus and cortex. In addition, the thymus is a fragile organ. Acute disease, tumor, high-dose irradiation or high-dose sterol can lead to rapid degeneration of thymus, and a large number of thymocytes die and fail. However, after the harmful factors are recovered or eliminated, the structure of thymus can gradually recover. If the thymus of newborn mice is removed, the animals will lack T cells and cannot reject the allograft. There are no secondary lymphoid nodules in peripheral lymphoid organs and lymphoid tissues, and the ability of the body to produce antibodies is also significantly reduced. If the thymus is removed a few weeks after the animal is born, a large number of virgin T cells have migrated to the surrounding lymphoid organs and tissues and have been able to exercise certain immune functions, so there is no effect in a short time, but the immunity of the body will gradually decline. If a piece of thymus is transplanted into a newborn animal with thymectomy, the immune deficiency of the thymectomy animal can be obviously improved.

There are abundant nerve endings in thymus, which terminate between thymocytes or near epithelial cells and macrophages. There are many neurotransmitter receptors on the surface of thymocytes, which indicates that nerves can regulate the development and differentiation of thymocytes. Thymus can secrete a variety of peptide substances, such as thymosin and thymopoietin, which can promote the differentiation and maturation of T cells. Prostaglandin (PG) is an important group of tissue hormones widely existing in animals and human bodies. The chemical structure of PG is generally 20-carbon unsaturated fatty acid with five-membered ring and two side chains. According to the different molecular structures, PG can be divided into type A, type B, type D, type E, type F, type H, type I and so on. Phosphorylation of cell membrane produces arachidonic acid, the precursor of PG, under the action of phospholipase A2. Under the catalysis of cyclooxygenase, arachidonic acid forms an unstable intramolecular peroxide, jujube PGG2, which is then converted into PGH2. Under the action of isomerase or reductase, PGH2 forms PGE2 or PGF2α, respectively. PGG2 and PGH2 can be converted into prostacyclin (PGI2) under the action of prostaglandin synthetase and thromboxane A2(TXA2) under the action of thromboxane synthetase (Figure 1 1-23). Fig. 1 1-23 synthetic pathways of main prostaglandins in vivo. In addition, arachidonic acid is synthesized by lipoxygenase. PG is metabolized very rapidly in the body, except PGI2, which is rapidly degraded and inactivated through the lung and liver. The half-life in plasma is 1-2 minutes. It is generally believed that PG is not a circulating hormone, but a tissue hormone that is locally produced and released in tissues to regulate local functions. The biological function of PG is extremely extensive and complex, which affects almost every system of the body. For example, TXA2 produced by platelets can aggregate platelets and constrict blood vessels. On the contrary, PHG2 produced by vascular intima can inhibit platelet aggregation and relax blood vessels. PGE2 can obviously inhibit gastric acid secretion, which may be a negative feedback inhibitor of gastric juice secretion. PGE2 can increase renal blood flow and promote sodium excretion and diuresis. In addition, PG has effects on thermoregulation, nervous system, endocrine and reproduction.

Adult thymus has important immune function.

Recently, researchers at the Southwest Medical Center of the University of Texas found that the thymus continues to play a role in adulthood and affects the recovery of patients receiving allogeneic stem cell transplantation. This paper was published in the latest issue of Blood Journal of American Blood Association. The researchers observed the effect of thymus after allogeneic bone marrow or stem cell transplantation in leukemia patients. These patients lost a lot of T cells due to chemotherapy. Dr DanielDouek, assistant professor of internal medicine at the Southwest Medical Center of the University of Texas, said: "Our question is: Does thymus really help to regenerate a new immune system after allogeneic transplantation? The result is affirmative, it regenerates a new immune system; Especially for children, the thymus contributes a lot. " Thymus produces t cells. T cells resist infection and help transplant patients recover. Then the researchers observed the main factors affecting thymus secretion. "The purpose is that if there is anything that can inhibit thymus secretion, we can try to prevent it clinically." We found that with the increase of age, the secretion of thymus decreased, as we expected. Most importantly, we found that graft-versus-host disease completely blocked the production of thymocytes. "If you want to rebuild a new immune system with a wide range of functions, you must find a way to eliminate graft-versus-host disease. He added that immunosuppressive drugs can treat graft-versus-host disease, and the researchers also found that those drugs did not inhibit thymus secretion. This means that graft-versus-host disease can be treated actively in the early stage without damaging thymus secretion. Douek said that the next step is to study the method of rebuilding the immune system, with the aim of developing various compounds for clinical experiments and laying the foundation for clinical experiments to promote immune system reconstruction. Previous studies showed that the thymus became active only in childhood, and then shrank. However, in 1998, researchers at the Southwest Medical Center of the University of Texas reported in Nature that the thymus constantly produced T cells throughout human life. Their research object is patients whose immune system is destroyed by HIV. In a study published in The Lancet magazine last year, researchers studied patients aged 34 to 66 who received autologous bone marrow transplantation (after chemotherapy) and found that their thymus regenerated their immune systems. Recent studies have involved patients who have received more common allografts. They are 67 patients from 4 medical centers, ranging from infants to adults.

Do you know who is the "king of immunity"?

At the upper end of the human sternum, between the left and right lungs, there is a yellow-gray tissue the size of a matchbox, which is the thymus. In the past, people regarded the thymus and appendix (cecum) as useless organs that had not completely degenerated during evolution. Over the past half century, with the progress of immunology, people have realized the important role of thymus in human immune function and praised it as the king of immunity. To know the king position of thymus in immunity, just look at the role of lymphocytes as the main force of specific immunity and their relationship with thymus.

70-80% of lymphocytes in blood are T lymphocytes (T cells for short). They were originally tiny white blood cells growing in bone marrow, which were sent to the thymus by blood. After being cultured by thymic hormone, they became mature T cells with no immune function, and then sent to organs such as spleen and lymphatic system, where they grew up under the action of thymic hormone, ready to resist all kinds of enemies harmful to human body. Thymic hormone can also improve the killing ability of lymphocytes and induce B cells (also a kind of lymphocytes) to mature.

T cells can be divided into:

Helper T cells can help activate B cells to produce antibodies, and also help killer T cells and macrophages to play their immune functions.

Inhibitory T cells can inhibit all kinds of T cells and B cells, regulate immune response and maintain immune homeostasis (i.e. immune tolerance).

Functional T cells are sensitized T cells that differentiate and proliferate after being stimulated by specific antigens. Can directly kill different things.

Memory T cells and memory B cells are lymphocytes that retain specific antigen information after initial stimulation, and their life span can be as long as several decades. When they are stimulated by the same antigen again, they can be divided into functional T cells that process antigens or plasma cells that produce antibodies.

Antibodies are necessary when killer T cells kill foreign bodies.

Natural killer T cells do not need antibodies and pre-sensitized lymphocytes to kill foreign bodies. It has immune monitoring function and plays an important role in killing tumors.

In embryonic stage, the thymus is bigger than the heart, even bigger than the lung, reaching the maximum in adolescence, then gradually degenerating, and decreasing to about 10g in middle age. Thymus tissue is gradually replaced by fat, and after 50 years old, the secretion of thymic hormone stops completely. Thymus, the king of immunity, was defeated after establishing and training an immune army.

Abnormal chest cavity can lead to elevated cholesterol.

A reporter from American Chinese Medicine Network (www.uschinahealth.com) reported that people always blame the increase of serum cholesterol on bad eating habits. I don't know that the content of serum cholesterol is closely related to a function called thymus on human neck.

Thymus secretes a series of hormones and participates in the metabolic regulation of organic substances including cholesterol. Experts pointed out that thymus disease is one of the main causes of hypercholesterolemia, second only to diet. 25% to 50% of people with low thymus function suffer from hypercholesterolemia in different degrees; On the contrary, 10% of hypercholesterolemia patients are accompanied by hypothyroidism. Therefore, when people suddenly find themselves suffering from hypercholesterolemia, they should first go to a doctor to check whether their thymus function is normal.

To this end, the American Association of Clinical Endocrinologists recently launched a program called "Controlling Cholesterol with Neck", aiming to let people know the connection between thymus and cholesterol.

People will produce auxin (HGH) during deep sleep, and its secretion is carried out by pulses. When people enter the age of 40, or when deep sleep is reduced due to mental stress and illness, the secretion of HGH will decrease or stop. Scientists have found that the secretion of HGH in people over 35 years old is nearly 75% lower than that in young people, which leads to the decline and contraction of various organs in the human body, and also leads to the happiness and fat accumulation of most people.

Biologists point out that human life expectancy should be 5-7 times that of sexual maturity. If the age limit is 20, people can live to 100- 140. But most people can't live to this age, mainly because the secretion of auxin decreases after the age of 35, which makes the organs of human organs atrophy, especially the thymus organs atrophy, which leads to the decline of immune function.

Medical research has proved that thymus is an important living organ of human body, which is located behind the sternal stalk, above the mediastinum and near the front of trachea. In the early stage of embryonic development, thymus and thyroid originated from the same source. After birth, the thymus grows rapidly and gradually moves to the back of the sternum. At birth, the thymus gland is about 65,438+05g. Because of the rich secretion of auxin in childhood, it reaches its peak in adolescence, making the thymus organs reach 30-40 grams. Thymus, which gradually degenerates in the future, is particularly sensitive to auxin (HGH). After the age of 35, the secretion of auxin decreases, so the thymus gradually degenerates. Therefore, thymus is an organ with a short life span in human body, which can be gradually replaced by adipose tissue after entering old age.

Thymus medulla microenvironment is an ideal place to cultivate T cells, and it is known as the guardian of human health. T cells have great skills in cellular immune response, which can directly kill pathogenic microorganisms, tumor cells and xenotoxins entering the human body. T cells are produced in bone marrow and are descendants of primitive blood cells (hematopoietic stem cells). Primitive blood cells migrate to thymus with blood circulation, proliferate and differentiate into lymphocytes, and the strong of these cells enter thymus medulla and grow healthily, obtaining the important function of cellular immunity.

But after the age of 35, the thymus gradually degenerated and finally died. Thymus degeneration is closely related to human aging, because after thymus atrophy, T cells in the human body are greatly reduced, and the immune system and immune function are also weakened, so the inhibition of B cells in the human body is also weakened a lot. B cells often do not produce antibodies as needed and attack normal cells indiscriminately, thus making people sick and causing immune system disorder. Modern medicine has proved that many senile diseases have a very important causal relationship with the decrease of T cells caused by thymus atrophy.

Retired Thymus: A Study on T Cell Generation, Sarah, Zhu Naishuo (School of Life Sciences, Fudan University, Shanghai 200433)

Thymus is the main place for T cell development. With the increase of age, thymus degenerates continuously. Classical theory holds that thymus only plays a role in the early stage of biological development. The latest discovery is that the thymus remains active after adulthood [1]. The progress of AIDS research strongly supports this view.

Development of 1 T cells in thymus

Thymus is the central immune organ where T cells differentiate and mature and receive educational choices. Thymus develops and matures in the early embryo, and it has been shrinking and degenerating since birth. The thymus of the elderly is full of adipose tissue and is considered inactive. Excision of thymus in early development will bring serious immune deficiency. Thymus secretes various cytokines to promote the maturation of T cells, and its epithelial cells are rich in various antigens, which provides an important microenvironment for the development of T cells.

T cell receptor (TCR) gene rearrangement occurs when CD4ˉCD8ˉ double negative T cells entering thymus develop into CD4+CD8+ double positive T cells. T cells meet the major histocompatibility complex (MHC) antigen of epithelial cells, accept positive selection, and acquire MHC restrictive recognition ability. T cells that have no MHC recognition ability are eliminated, and then CD4 or CD8 single positive T cells meet macrophages (mφ) and dendritic cells at the junction of cortical medulla, accept negative selection, and delete those T cells that react with autoantigens. The above process can delete more than 90% of thymocytes, and the remaining T cells enter the peripheral lymphatic circulation, which is called naive T cells, and further differentiate into effector T cells and memory T cells in the subsequent immune response [2].

With the development of organ transplantation and AIDS research, it is found that thymus can produce new newborn T cells in immune reconstruction, which is called thymus-dependent pathway. The main objection is that this kind of T cells are derived from peripheral T cell expansion, which is called thymus-independent pathway and has become a research hotspot in recent years.

2. A new method to study newborn T cells.

Analysis of recombinant products of (1) T cell gene developed by Douek et al.

TCR gene showed that αβTCR was the majority and γδTCR was the minority. The locus δ is located at the α site, between Vα and Jα, and TCRA and TCRB genes produce free loops of excised DNA fragments during rearrangement, that is, TCR rearrangement exclusion loops (TRECs). TRECs were completely excised on alleles and stably existed in T cells of peripheral tissues. Trecs does not participate in the replication of cell chromosome DNA, and is diluted with cell division. Therefore, the level of TRECS can reflect the recombinant activity of TCR gene in thymus and the proliferation efficiency of T cells outside thymus. The diversity of TCR rearrangement is inevitably accompanied by the diversity of TRECs. However, in all functional αβTCR gene rearrangements, TCRD at TCRA site must be excised, resulting in signal-linked Trec-SJ Trec and coding-linked Trec-CJTrec respectively, which can be used as universal markers of neonatal T cells [3].

Through this method, Douek's research team found that the level of TRECs decreased with age. Even if some subjects are 70 years old, the level of TRECs is still detectable, and the level of TRECs in patients with congenital thymic defects is always lower than that in normal people. It shows that thymus can continue to function until adulthood.

(2) The heavy hydrogen method developed by 2)McCune et al.

McCune et al. injected glucose labeled with heavy hydrogen into human body intravenously. Glucose is a precursor of deoxyribose, which can be mixed with DNA when T cells replicate. With the division of T cells, labeled DNA is constantly replaced by unlabeled DNA. By taking blood samples at different times, the productivity and average life span of T cells can be measured. McCune and others found that the life span of CD4T cells in AIDS patients was significantly shortened. After receiving highly active antiretroviral therapy (HAART), the production of T cells increased obviously, but their life span did not increase, which indicated that the regeneration of T cells played an important role in immune reconstruction [4].

(3) Thymectomy

Thymectomy is a traditional method to study thymus function, but it is still widely used at present. Haynes studied AIDS patients with thymectomy and without thymectomy, and found that the former showed some defects in immune reconstruction [5]. Berzines found that the output rate of T cells and the number of peripheral T cells remained unchanged in the transplantation of newborn thymus tissue, while the surface markers of newly transplanted peripheral thymocytes (RTEs) were different from those of established T cells, and the output rate of RTEs was consistent with that of thymocytes. Berzines believes that the thymus can continuously produce RTEs to replace the colonized T cells in peripheral tissues, thus maintaining the diversity of human T cell bank [6].

3. In the study of AIDS, it is found that thymus can rebuild human T cell bank.

(1)TRECs level analysis

Once the human body is infected with HIV, the level of TRECs will drop rapidly. After HAART treatment, with the reduction of HIV RNA copy number, the level of TRECs increased steadily, and the level of TRECs decreased accordingly after stopping treatment. In view of the fact that the proliferation of primary T cells is not so high and HIV is not sensitive to primary T cells, Douek thinks that the more likely explanation is that HIV destroys the function of thymus, inhibits the production of precursor thymocytes, or induces the death of CD4 T cells, thus reducing the production of primary T cells [1].

(2) Morphological observation of thymus in AIDS patients.

Autopsy of AIDS-related deaths showed that there was no active thymus tissue [5], thymocytes showed signs of death, and T cells expressing CD4 and CD8 were lacking in medulla [7]. McCune found that people newly infected with HIV have highly expressed thymus tissue, which indicates that thymus can respond to HIV infection. McCune believes that for some but not all patients, thymus function is even enhanced, and the death of T cells caused by HIV infection induces some thymus maturation mechanisms and awakens some residual dormant T cells [8].

Shteinman [9] and Bofil [10] believe that the real thymus is not filled with adipose tissue with age, nor with inflammatory cells in myasthenia gravis, but only exists in the peripheral vascular space and is buried in these tissues. Although their theory seems unacceptable, Haines thinks there is some truth. Two days before his death, CT examination of AIDS patients could find lymphoid tissue, but no similar active tissue was found in the subsequent autopsy. On the contrary, some peripheral infiltrating cells were found in vascular tissue. Haynes thinks that the lymphoid tissue shown by CT is just an illusion, but it is actually some infiltrated inflammatory cells. He put forward the hypothesis that thymus is composed of peripheral lymph components (existing in (3) an opposing theory)

The main opponents, such as Pakker, believe that the immune reconstruction of AIDS patients during treatment stems from the release of some isolated T cells during the redistribution of peripheral lymphoid tissue, because 98% of lymphocytes remain in peripheral lymphoid tissue. It is reasonable to think that most CD4 and CD8 T cells are captured by infected lymphoid tissues, which are inflamed due to strong cytotoxicity. Once HAART treatment reduces the viral load, inflammation will be relieved, cytotoxicity will return to normal level, and migrated T cells will be released [1 1].

The surface markers of mature T cells are different from those of newborn T cells. The former shows CD45+ RO++, while the latter shows CD45+ RA++. Supporters of this theory believe that the existence of newborn T cells can be detected in AIDS patients because of the inversion of the surface markers of mature T cells.

Pakker's research team also found that the re-proliferation of primary T cells produced by lymphoid tissue in peripheral circulation is a long process, and the increase of CD45+ra++ causes the re-proliferation of CD4+T cells, which can only be seen 12 months after the start of treatment, and the same phenomenon also occurs in bone marrow transplantation (BMT) [65400].

(4) Questioning the thymic independent pathway.

Douek believes that the immune reconstruction of AIDS patients should be attributed to the thymus-dependent pathway, because there is no data to support Pakker's claim that the withdrawal of cell banks exists. Douek can't detect the existence of TRECs in peripheral T cells of a few patients with congenital thymic dysplasia, which further proves that although pre-T cells may recombine TCR gene in lymph nodes, they certainly can't have a significant impact on the overall level of TRECs [3].

Haines studied AIDS patients with thymectomy and found that the recovery efficiency was significantly lower than that of patients without thymectomy. Hayens also found that before and after HAART treatment, the diversity of T cell bank in AIDS patients did not change significantly [5]. Considering Zhang et al.' s explanation of the mechanism of HAART-induced lymph node repair and lymphocyte T cell recovery [12] and Douek's conclusion, Haynes thinks that thymus and peripheral lymphoid tissue are equally important for the reconstruction of T cell bank, and that the proliferation of CD4+CD 45 ra ++ and CD4+T cells comes from a way independent of thymus from the beginning [5].

4. Evidence supporting thymus-dependent pathway was found in tissue transplantation.

The main evidence comes from bone marrow transplantation. Doumont-Girard found that in the first six months, almost all the growth of T cells came from the proliferation of peripheral T cells, expressing CD45+ro++ surface markers, and the diversity of TCR pool remained unchanged. CD4+Ra+ first appeared after 6 months. With the fluctuation of TCR library diversity, Dumont thought it was determined by the diversity of CD4+Ra+T cells. Obviously, CD4+Ra+T cells are new immigrants from thymus. In all patients, the recovery rate of T cells in adolescents is significantly higher than that in adults, which shows that thymus does play a certain role in immune reconstruction [13].

Mackall found in skin transplantation that female patients with thymectomy did not reject the new skin antigen of their male compatriots, and showed a decline in the general antigen response. Mackall believes that this phenomenon can not be explained only by the expansion of peripheral lymphocytes in immune reconstruction, but must be related to the continuous activity of thymus [8].

At present, the dispute between thymus-independent pathway and thymus-dependent pathway has not been satisfactorily resolved. Whether the difference of surface traces between CD45+ra++ and CD45+ro++ comes from the difference in manufacturing, or whether the latter turns the former upside down; Can HIV infect the chest?