Thymus: Definition, Morphology, Development, Involution, Functions, Location and Association with Diseases

It is a primary lymphoid organ and the initial site for the development of the immune function of T cells, it is morphologically similar in all species.

It is actually an epithelial organ in which its epithelial cells provide a framework containing T cells as well as a smaller number of other lymphoid cells.

There is a symbiotic interaction between the thymic microenvironment and developing T cells, and the specificity of T cell release into the systemic circulation is under thymic control.

The thymic cortex in a young animal is highly populated by developing T cells along with a minor proportion of associated epithelial cells.

Larger and more mature T cells are found in the marrow, where epithelial and other cell types are most abundant.

The thymus is a pyramid-shaped lymphoid organ that, in humans, is immediately below the sternum at the level of the heart.

This organ is called the thymus, because its shape resembles that of a thyme leaf.


The thymus divides into two lobes, located on either side of the body’s midline, and into smaller subdivisions called lobes.

It is covered by a dense capsule of connective tissue, which provides fibers to the body of the thymus for support.

The thymus tissue is distinguished into an external area, the cortex, and an internal area, the medulla.

The organ is mainly composed of two types of cells, called, respectively, lymphocytes and reticular cells.

The reticular cells form a loose mesh, as in a lymph node, while the spaces between them are filled with lymphocytes.

The cortex, which is characterized by its high concentration of lymphocytes, is the site where the greatest lymphocytic proliferation occurs.

The proliferation of lymphocytes in the thymus is uniformly distributed throughout the cortex, instead of the germinal centers, as occurs in other lymphoid tissues.

Some of the daughter cells, called T cells (derived from the thymus), that are produced in the cortex migrate to the marrow, where they enter the bloodstream through the medullary veins, adding to the lymphocytes seen in the peripheral blood and lymphoid organs.

Description of the development

Stieda in 1881 was the first to observe that the epithelial cells of the thymus gland originated from a visceral pouch, the third endoderm of the pharyngeal pouch.

Currently this theory is maintained that like the parathyroid, the thymus derives from the third pharyngeal bags.

The development is a series of inductive epithelial and mesenchymal interactions between the arc mesenchyme derived from the neural crest and the endoderm of the bursa.

There is also the possibility that the superficial ectoderm of the third pharyngeal clefts participates in the development of the thymus.

But those theories that have been discussed more recently, about the possible contribution of the superficial ectoderm, the ectoderm of the third pharyngeal cleft have been denied by tracing studies with mice.

Hassall’s bodies form between 6 and 10 months.

They appear after lymphopoiesis has been established and the cortex, medulla, and cortico-medullary junction can select for progressively maturing T lymphocytes.

Experimental studies have shown that a contribution from the neural crest is also required during early thymic organogenesis.

Involution of the thymus

Unlike most other lymphoid structures, the thymus grows rapidly and reaches its largest size relative to the rest of the body during fetal life and the first few years after birth.

Thereafter, it continues to grow, but more slowly than the other organs.

At the beginning of puberty, the thymus begins a slow process of reduction.

This gradual decrease in size continues for the rest of the individual’s life and slows down into adulthood.

The involution of the thymus is a postnatal process defined as a decrease in the size, weight and activity of the gland with advancing age.

After puberty, much of the thymus parenchyma is replaced by adipose tissue, particularly cortical lymphoid tissue.

During involution, or shrinkage, of the thymus, the cortex becomes thin.

The lymphocytes disappear and are replaced by fatty tissue from the partitions between the lobes. And there is an increase in the size of the thymic corpuscles.

This process of involution of the thymus is under the control of steroid hormones.

A review of the time course of this process in humans has been carried out and the regression leads to a decrease in the T cells generated, modifying the composition of the set of peripheral T cells and altering their phenotype and function.

Thymic involution has been described as the result of high levels of circulating sex hormones, particularly during puberty, and a smaller population of bone marrow precursor cells and eventually changes in the thymic microenvironment.

The involution process is never complete, and the pieces of thymus tissue that remain are probably enough to maintain its function.


The functions of the thymus that have been observed so far are primarily related to the newborn.

Removal of the organ in the adult has little effect, but when the thymus is eliminated in the newborn, T cells in the blood and lymphoid tissue are depleted, and failure of the immune system causes a disease of gradual and fatal wasting.

The individual whose thymus is removed at birth is less able to reject foreign tissue grafts or to produce antibodies against certain antigens.

Also, certain parts of the white pulp of the spleen and lymph nodes are reduced in size.

These results demonstrate that T cells produced in the thymus and transported to lymphoid tissues are crucial elements in the development of immunity.

It is known that most of the lymphocytes that are produced in the thymic cortex die without leaving the organ.

Since the T cells that leave the thymus are equipped to react against foreign antigens, it is assumed that the thymus destroys the lymphocytes that are involved in an autoimmune reaction, including, they would react against the individual’s own tissues.

The thymus differs structurally from other lymphoid organs in that it does not have lymphatic vessels draining into it.

It is not a filter like the lymph nodes, which are positioned so that microorganisms and other antigens are exposed to your cells.

Thymic lymphocytes are sealed off from the rest of the body by a continuous layer of epithelial cells, which completely surround the organ.

While sequestered, lymphocytes differentiate or acquire the abilities to perform specialized tasks.

It has even been suggested that the hormonal functions of the thymus help in this differentiation.

Of these specialized lymphocytes, the helper T cells work synergistically with the independent lymphocytes of the thymus (B cells) to produce antibodies.

Cytotoxic T cells directly attack invading microorganisms and foreign tissue, such as organ transplants.

The thymus is essential for the normal development in mammals of the system responsible for immune responses.

Research has shown that its elimination in newborn mice results in a deficiency of a type of white blood cells (lymphocytes) and the consequent probability of early death from infection.

Preparations of thymus glands of various species contain a protein component, called Thymosin, which promotes the development of lymphocytes.

Although thymosin is sometimes considered as a possible thymus hormone, the evidence is not yet complete.

Location of the adult thymus

The thymus is an organ with a flat structure and a soft consistency located in the thoracic cavity, between two organs: the heart and the sternum.

The thymus plays a key role in the development of an effective immune system, as well as endocrine function.

In the adult thymus, specialized microenvironments allow the production of self-tolerant T cells from immature precursors.

The thymus has two origins for lymphoid thymocytes and thymic epithelial cells.

Thymus cells

The mature thymic epithelium has two main cell types: cortical thymic epithelium and medullary thymic epithelial cells or stromal cells.

These thymic stromal cells provide signals for T cell differentiation.

  • The cortical thymic epithelium.
  • Medullary thymic epithelial cells.
  • Adipose tissue.
  • T cells
  • Macrophages of the thymus.
  • Hassall’s corpuscles.

Thymus cells are epithelial reticular cells, with abundant cytoplasm, a large nucleus, ovoid in shape and with 1 to 2 nucleoli.

Cortical thymic epithelium acts in the early stages of T-cell development, is committed to positive selection, helps lymphocytes mature.

Medullary thymic epithelial cells are involved in the negative selection and induction of regulatory T cells.

Lymphocytes are scarcer and smaller in the marrow.

Lymphocytes pass to the thymus and by stimulation of thymic hormones are differentiated into T cells.

T cell maturation occurs through interaction with thymic epithelial cells in different microenvironments and regions of the thymus lobe, hence its name.

T-cell progenitors enter the thymus at the border of the cortical thymic epithelium and into the medulla through postcapillary venules.

These migrate into the capsule in response to chemokine signaling.

In the cortex, thymocytes are selected positively by cortical thymic epithelium and then migrate to the medulla.

In the marrow, thymocytes are screened for their reactivity to restricted tissue autoantigens expressed by medullary thymic epithelial cells.

Mature T cells exit the thymus through blood or lymphatic vessels in response to a gradient of sphingosine-1-phosphate (S1P).

The T cells of the immune system are essential for responses against infections and much research concerns the postnatal development of T cells within the thymus.

Thymus macrophages, or phagocytes, are derived from the same lineage as monocytes in bone marrow.

They are located in the cortex and medulla, but they are more numerous (denser) in the medulla. They are histologically difficult to distinguish.

Hassall’s bodies, also called Hassall’s corpuscles.

These bodies are named after Arthur Hill Hassall (1817-1894), a British physician and chemist.

These corpuscles, existing only in the thymus, are concentric layers of epithelial cells, express thymic stromal lymphopoietin, suggesting that Hassall’s corpuscles play a critical role in dendritic cell-mediated secondary selection of medium to high affinity autoreactive T cells. , leading to the generation of CD4 (+) CD25 (+) regulatory T cells within the thymus.

Thymic stromal lymphopoietin is a cytokine derived from epithelial cells that is expressed in various tissues (skin, intestine, lungs, and thymus) that communicate through a thymic stromal lymphopoietin receptor.

The adipose tissue is the tissue that replaces the parenchyma as the involution of the thymus progresses.

Association with diseases

There has been a report showing changes in Hassall’s body morphology associated with congenital heart defects.

Current research has found tissue-specific autoantigens in these Hassall’s thymic corpuscles and revealed that they are associated with the pathogenesis of diseases such as: type 1 diabetes, rheumatoid arthritis, multiple sclerosis, autoimmune thyroiditis, Goodpasture syndrome, among other.

T-cell-related diseases are:

  • Severe combined immunodeficiency.
  • Syndrome of Omenn.
  • Acquired immunodeficiency syndrome.
  • DiGeorge syndrome.
  • Chromosome break syndromes.
  • B-cell and T-cell disorders, such as: ataxia telangiectasia and Wiskott-Aldrich syndrome.
  • T-cell lymphoma.