Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole.
The primary role of the thymus is to provide mature T cells for the peripheral immune system. The mechanisms involved in the cellular export processes are as yet unknown. In this study, we examined the ability of 2-acetyl-4-tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia caramel food colouring, to inhibit T-cell export from the thymus. BALB/c mice were maintained on drinking water containing THI for 5 days. The mice showed a twofold increase in the total number of mature medullary thymocytes (CD4+CD8- and CD4-CD8+) as well as a slight decrease in the total number of immature double-positive cells (CD4+CD8+). The mature single-positive thymocytes were found to express high levels of the homing molecule L-selectin, suggesting that these potential emigrants were prevented from leaving the thymus. To confirm this, THI-treated mice were injected intrathymically with fluorescein isothiocyanate and the number of labelled T cells appearing in the lymph nodes and spleen was determined 16 hr later. A 10-fold decrease in the number of CD4+ and CD8+ recent thymic emigrants in the lymph nodes and spleen of THI-treated mice was observed. Previous studies have shown that THI does not affect other aspects of thymocyte development, such as proliferation and differentiation. Taken together, these results suggest that the immunosuppressive effects of THI may be due, in part, to preventing of the final step of T-cell export out of the thymus.
Gugasyan
R
R
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, NSW, Australia.
Coward
A
A
O'Connor
L
L
Shortman
K
K
Scollay
R
R
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D007093:Imidazoles; D007166:Immunosuppressive Agents; D019041:L-Selectin; C049929:2-acetyl-4(5)-tetrahydroxybutylimidazole