Cellular mechanism of thymic involution

Scand J Immunol. 2003 May;57(5):410-22. doi: 10.1046/j.1365-3083.2003.01206.x.


Involution of the thymus and alterations in the development of thymocytes are the most prominent features of age-related immune senescence. We have carried out a comparative analysis of thymocyte and stroma in rapid thymic involution DBA/2 (D2) strain of mice compared with slow involution C57BL/6 (B6) strain of mice. Analysis of mice at 15 months of age suggested an age-related decrease in the thymocyte cell count, a block in the development of T cells and cortical involution in D2 mice compared with 3-month-old mice. TUNEL (terminal-deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling) staining and fluorescence-activated cell sorter (FACS) analysis showed that there was a significant increase in apoptotic cells in the cortex region of thymus in 15-month-old D2 mice compared with the same aged B6 mice. The thymocyte proliferation rate, as assessed by bromodeoxyuridine (BrdU) staining and [3H]-thymidine incorporation assay, was lower in 3-month-old D2 mice compared with the same age B6 mice. Immunohistochemical staining showed that the arrangement of MTS (mouse thymus stromal)-10+ epithelial cells and MTS-16+ connective tissue staining pattern had become disorganized in 15-month-old D2 mice but remained intact in B6 mice of the same age. These results suggest that, in D2 mice, both the thymocytes and stromal cells exhibit age-related defects, and that the genetic background of mice plays an important role in determining age-related alterations in thymic involution.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / immunology*
  • Aging / pathology
  • Animals
  • Apoptosis*
  • Cell Division
  • Connective Tissue / ultrastructure
  • Extracellular Matrix / ultrastructure
  • Female
  • In Situ Nick-End Labeling
  • Lymphocyte Activation
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Stromal Cells / ultrastructure
  • T-Lymphocyte Subsets / cytology
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology