Cellular Mechanism of Thymic Involution

AbstractInvolution 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.