Analysis of the human thymic perivascular space during aging
Kristina G. Flores, Jie Li, Gregory D. Sempowski, Barton F. Haynes, Laura P. Hale
Kristina G. Flores, Jie Li, Gregory D. Sempowski, Barton F. Haynes, Laura P. Hale
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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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Phenotypically immature thymocytes are present in adult thymus tissues m...
Phenotypically immature thymocytes are present in adult thymus tissues meeting immunohistologic criteria for thymopoiesis. Lymphocytes from a 78-year-old male thymus were analyzed by flow cytometry using combinations of fluorescently labeled mAb’s. The majority of lymphocytes present were CD3+ (a), with 82% CD4+, CD8+ double-positive (b). 3% of cells were reactive with CD19 and CD20 mAb’s (c), and were consequently identified as B lymphocytes. Of the CD4hi cells, more than 90% were CD45RO+ (d), 97% were CD38+ (e), and 97% were CD45RA– (f), consistent with an immature phenotype. Similar results were seen with gating on CD8+ lymphocytes. Very few mature T cells were present in this sample, consistent with the observed lack of lymphocytes infiltrating the PVS on immunohistochemical sections. Although the majority of cells present in this thymus were immature thymocytes, the absolute numbers of thymocytes obtained for analysis were less than 1% of those obtained per gram of tissue from pediatric thymus.