EMIGRATION OF MATURE T-CELLS FROM 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 pe ripheral 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 a s a component of ammonia caramel food colouring, to inhibit T-cell exp ort from the thymus. BALB/c mice were maintained on drinking water con taining THI for 5 days. The mice showed a twofold increase in the tota l number of mature medullary thymocytes (CD4(+)CD8(-) and CD4(-)CD(+)) as well as a slight decrease in the total number of immature double-p ositive cells (CD4(+)CD8(+)). The mature single-positive thymocytes we re found to express high levels of the homing molecule L-selectin, sug gesting that these potential emigrants were prevented from leaving the thymus. To confirm this, THI-treated mice were injected intrathymical ly 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 emig rants 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. Take n together, these results suggest that the immunosuppressive effects o f THI may be due, in parr, to preventing of the final step of T-cell e xport out of the thymus.