Characterization and mechanisms of thymic atrophy in protein-malnourished mice: role of corticosterone.
The purpose of this project was to characterize changes in murine T lymphocyte subpopulations during thymic atrophy induced by protein malnutrition and to determine the role of elevated serum corticosterone in this process. A suitable animal model was generated by placing mice on protein-sufficient (PS) and protein-deficient (PD) diets for 6 weeks. Body weight was monitored to determine the establishment and maintenance of malnutrition. Results obtained using PD mice indicated a direct correlation between serum corticosterone levels and thymic atrophy. Furthermore, results of the experiments using mice implanted with corticosterone-impregnated pellets indicated that corticosterone alone, at the levels observed in PD mice, induced thymic atrophy in normal mice. These results demonstrate that the thymic atrophy induced by protein malnutrition is primarily due to elevated serum corticosterone. As indicated by flow cytometric analysis, the number of cells in all thymocyte subpopulations decreased as protein malnutrition continued, possibly reflecting depletion of immature CD4-/CD8- and CD4+/CD8+ cells, ultimately resulting in loss of mature CD4+ and CD8+ cells. TCR expression by PD thymocytes, especially those with high levels of CD3, increased during the dietary period. Mice implanted with corticosterone pellets experienced severe losses of CD4+/CD8+ cells, resulting in thymocyte subpopulation and CD3 profiles more similar to those of hydrocortisone-injected mice than those of PD mice. Therefore, whereas thymic atrophy in protein-malnourished mice seems to be caused by elevated serum corticosterone, it appears that additional factors further modulate thymocyte proliferation, differentiation, and/or death in this system.
Barone
K S
KS
Department of Microbiology, Miami University, Oxford, Ohio 45056.
O'Brien
P C
PC
Stevenson
J R
JR
D000818:Animals; D001284:Atrophy; D002452:Cell Count; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D011488:Protein Deficiency / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000473:pathology*
D003345:Corticosterone