The influence of FK-506 on the thymus and spleen in normal C3H/He mice: flow cytometric analysis of lymphocyte subpopulations.
Although FK-506 has been widely investigated as a potent suppressor of organ allograft rejection in animals, little is known about the effect of FK-506 on normal animals. In this study, we investigated the influence of FK-506 on the thymus and spleen in normal C3H/He mice at the age of 5 weeks. Mice were given dosages of FK-506 varying between 0.3 and 30 mg/kg/day intramuscularly for 5 days. After treatment with FK-506, the total number of lymphocytes in the thymus was significantly decreased in a dose-dependent manner; however, no change was evident in the total number of lymphocytes in the spleen. FK-506 also influenced the immunophenotypes in thymocytes, but not in splenocytes. The absolute number of CD4+ CD8- or CD4- CD8+ thymocytes decreased significantly in the 0.3 mg/kg/day-treated group. CD4+ CD8-, but not CD4-CD8+ thymocytes decreased further in the 1 mg/kg/day-treated group. Neither subpopulation decreased any further with continuing administration. On the other hand, the number of CD4+ CD8+ thymocytes did not decrease significantly in the 0.3 mg/kg/day-treated group, whereas it did decrease significantly in the 1 mg/kg/day-treated group, decreased further with the increase in dosage of FK-506, and decreased markedly in the 30 mg/kg/day group, The number of CD4-CD8-thymocytes did not show any change, even in the high-dosage groups. These results indicate that FK-506 influences the subpopulations of thymocytes according to its dosage. At a lower dosage, it affects mature CD4+ CD8- or CD4- CD8+ cells, but not immature CD4+ CD8+ and CD4-CD8- cells.2
Chen
M F
MF
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Suzuki
H
H
Maruyama
M
M
Yano
S
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D016130:Immunophenotyping; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D016559:Tacrolimus