The effect of age on thymic function

Abstract

Age-related regression of the thymus is associated with a decline in naïve T cell output. This is thought to contribute to the reduction in T cell diversity seen in older individuals and linked with increased susceptibility to infection, autoimmune disease, and cancer. Thymic involution is one of the most dramatic and ubiquitous changes seen in the aging immune system, but the mechanisms which underlying this process are poorly understood. However, a picture is emerging, implicating the involvement of both extrinsic and intrinsic factors. In this review we assess the role of the thymic microenvironment as a potential target that regulates thymic involution, question whether thymocyte development in the aged thymus is functionally impaired, and explore the kinetics of thymic involution.

Keywords: immunosenescence; thymic involution; thymic stroma; thymocyte; thymus.

Figure 1

The effect of age on thymic function. Schematic diagram outlining the pathway of T cell development. Aging can impact on variety of pathways during the development of T cells. With increasing age HSC appear to have a reduced lymphoid potential and increased myeloid differential capacity. Age-related involution is associated with reduced thymic mass and altered architecture resulting in reduced thymic output in the aged thymus. In the young, T cell development is functional and the peripheral T cell is pool is diverse; as depicted by the various colors. Furthermore, normal thymopoiesis provides a positive effect on thymic structure; thymic cross-talk. In contrast, T cell output is significantly reduced in the aged thymus resulting in loss of diversity and alteration in the phenotype and function of peripheral T cells; with the majority of cells being in the memory pool. Modifications in the thymic microenvironment are likely to have an impact on thymopoiesis resulting in defective RTE, which in turn disrupt thymic cross-talk leading to further alteration of TEC structure. Immunofluorescence image of young (6 weeks) and old (18 months) murine thymus stained with anti-keratin antibody (55) which detects cortical (C) and medullary (M) TEC. In the young thymus, antibody staining shows the cortical epithelium as a network of long thin processes, while the medullary region reveals a squamous appearance. In contrast, the staining on old thymic section revealed a reduced network of cortical epithelial cells, the medullary region is smaller and more diffuse while the cortical-medullary junction is less distinctive; as also depicted in the schematic. C, cortex; M, medulla. Picture (100× magnification).