Hassall’s Corpuscles (HC) are structures unique to the thymus, a specialized organ positioned in the chest that serves as a training ground for immune cells. These structures are found exclusively in the inner region of the thymus, known as the medulla. Their function is linked to the maturation of T-cells, a type of white blood cell responsible for adaptive immunity. HC contribute to the body’s ability to distinguish between its own tissues and foreign invaders.
Anatomy and Cellular Composition within the Thymus
Hassall’s Corpuscles are identifiable by their characteristic appearance, which often resembles an onion sliced in half. They are formed by concentric layers of specialized cells. The primary cell type composing these structures is the medullary thymic epithelial cell (mTEC), which undergoes terminal differentiation to form the corpuscles.
These mTECs arrange themselves around a central core that can contain cellular debris, granular cells, and signs of keratinization, similar to what is seen in skin cells. The size of these bodies is variable, ranging from about 20 to over 100 micrometers in diameter, and they typically grow larger and more complex as a person ages. Most HC are heterocellular, meaning they also incorporate other cell types from the surrounding tissue, such as macrophages, dendritic cells, and lymphocytes.
Mediating Central Immune Tolerance
The role of HC is their participation in “central tolerance,” a mechanism that prevents the immune system from attacking the body’s own tissues. Immature T-cells, called thymocytes, migrate through the thymus and must pass a rigorous selection process to ensure they are functional but not self-reactive. HC, along with other medullary cells, are situated where this selection occurs.
One outcome of this process is the elimination of T-cells that react too strongly to the body’s own proteins, known as negative selection. If a developing T-cell’s receptor binds with high affinity to a self-antigen presented in the medulla, the cell is signaled to undergo programmed cell death. This deletion prevents future autoimmune attacks.
A second outcome is the promotion of regulatory T cells (Tregs), which are specialized immune cells that actively suppress immune responses. A subset of T-cells with a specific level of self-reactivity is diverted to become Tregs, which express the transcription factor FOXP3. These cells leave the thymus equipped to patrol the body and restrain any self-reactive T-cells that may have escaped negative selection.
Secreted Factors Guiding T-Cell Development
Hassall’s Corpuscles influence T-cell development by releasing specific signaling molecules into the local environment. Medullary thymic epithelial cells within the corpuscles are a source of Thymic Stromal Lymphopoietin (TSLP), a cytokine that acts on other cells in the medulla. TSLP activates local dendritic cells, instructing them to promote the differentiation of immature T-cells into regulatory T cells.
Another molecule involved is Interleukin-7 (IL-7), a cytokine produced by thymic epithelial cells that is required for the survival, proliferation, and differentiation of various T-cell subsets. The IL-7 receptor is shared by TSLP, suggesting an overlapping pathway where both signals contribute to the development of Tregs in the thymus. The combined action of TSLP and IL-7 signaling is required for the full development of the Treg cell population.
Dysfunction and Autoimmunity
A failure in the central tolerance mechanism mediated by Hassall’s Corpuscles and mTECs has consequences for human health. When the selection or instruction of T-cells is compromised, self-reactive T-cells can escape the thymus, leading to autoimmune diseases. This breakdown is implicated in conditions such as Type 1 diabetes, multiple sclerosis, and rheumatoid arthritis.
With age, the thymus naturally undergoes involution, where its tissue is progressively replaced by fat and its function declines. This age-related shrinking impacts the overall activity of the HC, leading to a decline in their number and functional capacity over time. This decline contributes to the increased susceptibility to autoimmune disorders and a general weakening of the immune system observed later in life.