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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.

Adjuvant-induced arthritis (AA) in Lewis rats is a widely used model of chronic inflammatory arthritis. Non-articular features such as weight loss and necrotizing granulomas of the spleen and lymph nodes also occur in this model. The compound 2-acetyl-4-tetrahydroxybutylimidazole (THI) marginally delayed the development of AA. However, this agent had no effect on the incidence or severity of disease. In contrast, THI totally prevented granuloma formation in the spleen and associated splenomegaly. We conclude that THI may be a useful adjunctive agent for some inflammatory diseases.

The compound 2-acetyl-4-tetrahydroxybutylimidazole (THI) is known to suppress a contact hypersensitivity (CH) response. The effect of THI on lymphocyte subsets during treatment and in a CH response has not been shown in mice. To further define the immunosuppressive potential of THI, a time-course study during the CH response to oxazolone (OX) was performed. While THI can prevent the induction of CH, if treatment is started before sensitization, it has a low therapeutic capability since it could not significantly inhibit the response when continuous oral treatment was commenced during the course of CH. We report that during this response continuous oral treatment of non-obese diabetic (NOD) mice with THI reduced the number of CD4+ and CD8+ T cells in the peripheral blood. In the draining lymph nodes THI treatment had no effect on lymphocyte subsets prior to contact sensitization, but subsequent sensitization and elicitation with OX could not stimulate a significant increase in the number of CD4+ T cells in the treated mice, whereas untreated control mice showed elevated numbers of these lymphocytes. These findings suggest that THI can inhibit an CH response by preventing the recruitment of CD4+ T cells in the draining lymph nodes through an unknown mechanism.