Early block in maturation is associated with thymic involution in mammary tumor-bearing mice.
We previously reported that mice implanted with mammary tumors show a progressive thymic involution that parallels the growth of the tumor. The involution is associated with a severe depletion of CD4+8+ thymocytes. We have investigated three possible mechanisms leading to this thymic atrophy: 1) increased apoptosis, 2) decreased proliferation, and 3) disruption of normal thymic maturation. The levels of thymic apoptosis were determined by propidium iodide and annexin V staining. A statistically significant, but minor, increase in thymic apoptosis in tumor-bearing mice was detected with propidium iodide and annexin V staining. The levels of proliferation were assessed by in vivo labeling with 5'-bromo-2'-deoxyuridine (BrdU). The percentages of total thymocytes labeled 1 day following BrdU injection were similar in control and tumor-bearing mice. Moreover, the percentages of CD4-8- thymocytes that incorporated BrdU during a short term pulse (5 h) of BrdU were similar. Lastly, thymic maturation was evaluated by examining CD44 and CD25 expression among CD4-8- thymocytes. The percentage of CD44+ cells increased, while the percentage of CD25+ cells decreased among CD4-8- thymocytes from tumor-bearing vs control animals. Together, these findings suggest that the thymic hypocellularity seen in mammary tumor bearers is not due to a decreased level of proliferation, but, rather, to an arrest at an early stage of thymic differentiation along with a moderate increase in apoptosis.
Adkins
B
B
Department of Microbiology and Immunology, University of Miami Medical School, Miami, FL 33136, USA.
Charyulu
V
V
Sun
Q L
QL
Lobo
D
D
Lopez
D M
DM
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001284:Atrophy; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D016130:Immunophenotyping; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D018960:Hyaluronan Receptors