Cellular mechanism of thymic involution.
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.
Li
L
L
Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hsu
H-C
HC
Grizzle
W E
WE
Stockard
C R
CR
Ho
K-J
KJ
Lott
P
P
Yang
P-A
PA
Zhang
H-G
HG
Mountz
J D
JD
William
G E
GE
D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D003238:Connective Tissue / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000648:ultrastructure; D005260:Female; D020287:In Situ Nick-End Labeling; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017154:Stromal Cells / Q000648:ultrastructure; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology