Analysis of the human thymic perivascular space during aging
Kristina G. Flores, … , Barton F. Haynes, Laura P. Hale
Kristina G. Flores, … , Barton F. Haynes, Laura P. Hale
Published October 15, 1999
Citation Information: J Clin Invest. 1999;104(8):1031-1039. https://doi.org/10.1172/JCI7558.
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Article

Analysis of the human thymic perivascular space during aging

Abstract

The perivascular space (PVS) of human thymus increases in volume during aging as thymopoiesis declines. Understanding the composition of the PVS is therefore vital to understanding mechanisms of thymic atrophy. We have analyzed 87 normal and 31 myasthenia gravis (MG) thymus tissues from patients ranging in age from newborn to 78 years, using immunohistologic and molecular assays. We confirmed that although thymic epithelial space (TES) volume decreases progressively with age, thymopoiesis with active T-cell receptor gene rearrangement continued normally within the TES into late life. Hematopoietic cells present in the adult PVS include T cells, B cells, and monocytes. Eosinophils are prominent in PVS of infants 2 years of age or younger. In the normal adult and the MG thymus, the PVS includes mature single-positive (CD1a– and CD4+ or CD8+) T lymphocytes that express CD45RO, and contains clusters of T cells expressing the TIA-1 cytotoxic granule antigen, suggesting a peripheral origin. PBMCs bind in vitro to MECA-79+ high endothelial venules present in the PVS, suggesting a mechanism for the recruitment of peripheral cells to thymic PVS. Therefore, in both normal subjects and MG patients, thymic PVS may be a compartment of the peripheral immune system that is not directly involved in thymopoiesis.

Authors

Kristina G. Flores, Jie Li, Gregory D. Sempowski, Barton F. Haynes, Laura P. Hale

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Figure 1

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Thymic PVS increases with age in normal individuals and in patients with...
Thymic PVS increases with age in normal individuals and in patients with MG. The percent thymic PVS determined from H&E–stained sections is shown as a function of age quintile. (a) Data for normal individuals are expressed as mean ± SD for the indicated number of cases. Quintile 1: 7 ± 2%, n = 18; quintile 2: 12 ± 7%, n = 19; quintile 3: 37 ± 19%, n = 10; quintile 4: 55 ± 18%, n = 21; quintile 5: 82 ± 16%, n = 19. (b) Data for patients with MG are expressed as mean ± SD for the indicated number of cases. Quintile 2: 23 ± 13%, n = 2; quintile 3: 61 ± 34%, n = 8; quintile 4: 83 ± 14%, n = 13; quintile 5: 96 ± 2%, n = 8. (c–h) Cytokeratin immunoperoxidase staining (brown color) outlines TES, with an H&E counterstain. Letters denote representative regions of thymic cortex (C), medulla (M), and PVS (P). (c) Quintile 1. (d) Quintile 2. (e) Quintile 3. (f) Quintile 4. (g) Quintile 5. (h) Thymus with follicular hyperplasia from a 20-year-old female with MG. Cytokeratin and H&E staining shows that primary and secondary follicles are located outside the cytokeratin network, within the PVS. ×25 (original magnification).