Evolution of the thymus size in response to physiological and random events throughout life

Microsc Res Tech. 2003 Dec 15;62(6):464-76. doi: 10.1002/jemt.10408.

Abstract

During embryogenesis and in the early stages of life, the thymus is a crucial organ for the generation of the T cell repertoire. T cells are generated from hematopoietic stem cells already differentiated to precursor T cells in the bone marrow. These cells enter the thymus guided by chemotactic factors secreted by this organ. The complex maturation process takes place that ensures self-tolerance and homeostasis. Thymocytes that show autoreactivity do not leave the thymus, but rather die by apoptosis. The final percentage of mature T cells that survive to migrate from the thymus to the periphery is very low: at most 5%, under optimal conditions. The highest migration occurs in childhood and adulthood, at least in mice and humans; however, it declines throughout life and is minimal in the elderly. Under normal circumstances, the thymus commences involution soon after birth, and this involution correlates with the capacity to export mature T cells to the periphery. Hormones, cytokines, and neurotransmitters all play a role in this age-associated process, but the reasons for and mechanisms of this involution remain unknown. Apart from physiological conditions that change throughout life and govern age-related thymus evolution, random states and events provoked by intrinsic or extrinsic factors can induce either thymus involution, as in reversible transient thymic hypoplasias, or thymic hyperplasias. The age-associated involution, unlike transient involutions, follows a regular pattern for all individuals, though there are clear differences between the sexes. Nevertheless, even the age-associated involution seems to be reversible, raising the possibility of therapeutic strategies aimed at enhancing thymus function in the elderly.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological*
  • Aging / physiology*
  • Animals
  • Biological Evolution
  • Cell Differentiation
  • Female
  • Heat-Shock Response
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Size
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / physiology*