Cellular mechanism of thymic involution.

Academic Article

Abstract

  • 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.
  • Published In

    Keywords

  • Aging, Animals, Apoptosis, Cell Division, Connective Tissue, Extracellular Matrix, Female, In Situ Nick-End Labeling, Lymphocyte Activation, Lymphocyte Count, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Stromal Cells, T-Lymphocyte Subsets, Thymus Gland
  • Author List

  • Li L; Hsu H-C; Grizzle WE; Stockard CR; Ho K-J; Lott P; Yang P-A; Zhang H-G; Mountz JD
  • Start Page

  • 410
  • End Page

  • 422
  • Volume

  • 57
  • Issue

  • 5