Hassall’s Corpuscles are distinctive, concentric clusters of epithelial cells found within the thymus, an organ central to the body’s immune system. Also known as thymic corpuscles, they were discovered in 1846. While their exact mechanisms are still being fully explored, their presence suggests important functions in immune development.
Anatomy and Location
Hassall’s Corpuscles are located within the medulla of the thymus gland, an organ situated in the upper chest behind the breastbone. These structures are formed from type VI thymic epithelial cells, arranged in concentric layers. This arrangement often creates a central core that can appear keratinized or degenerated.
Microscopically, these corpuscles appear as spherical or ovoid bodies. Their size can vary, with diameters ranging from approximately 20 to over 100 micrometers. The epithelial cells comprising these corpuscles contain keratohyalin and bundles of cytoplasmic fibers.
Role in Immune System Development
Hassall’s Corpuscles contribute to T-cell maturation and selection within the thymus. This process, known as thymic education, teaches T-cells to distinguish between the body’s own components (“self”) and foreign invaders (“non-self”). Regulatory T-cells (Tregs), which prevent autoimmune reactions, are influenced by these corpuscles.
The corpuscles achieve this influence through the secretion of signaling molecules, including cytokines and chemokines. For instance, they are a source of thymic stromal lymphopoietin (TSLP), a cytokine that directs the maturation of dendritic cells. These activated dendritic cells, in turn, enhance the conversion of immature T-cells into Foxp3+ regulatory T-cells.
Other cytokines like IL-4 and IL-7 also play a part in this environment. These interactions contribute to the expression of autoantigens by medullary thymic epithelial cells (mTECs), which are closely associated with Hassall’s Corpuscles. The presentation of these self-antigens allows developing T-cells to undergo a selection process, where those that react strongly to self-antigens are eliminated, thereby promoting central tolerance and preventing autoimmunity.
Changes with Age and Disease
Hassall’s Corpuscles undergo changes throughout an individual’s lifespan, particularly with thymic involution. This natural process involves the gradual shrinking and functional decline of the thymus with age, which typically begins as early as one year of age in humans. As the thymus involutes, its functional tissue is progressively replaced by adipose (fatty) tissue, impacting overall immune function.
The morphology and number of Hassall’s Corpuscles can be altered during this age-related decline. While they tend to grow larger with age, their overall contribution to the thymic microenvironment may diminish as the thymus atrophies. This reduction in thymic output of new T-cells can lead to a decreased diversity of T-cells in the periphery, potentially affecting the immune system’s ability to respond to new threats in older individuals.
Beyond natural aging, changes in Hassall’s Corpuscles have been observed in various pathological conditions. In autoimmune diseases such as Myasthenia Gravis and Systemic Lupus Erythematosus, alterations in the number or morphology of these corpuscles have been noted. For example, patients with Myasthenia Gravis and Hashimoto’s thyroiditis have shown particular morphological changes in Hassall’s Corpuscles, including calcification or cystic dilatations. Researchers have also found tissue-specific self-antigens within Hassall’s Corpuscles, suggesting their involvement in the development of autoimmune conditions like type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.