THE IMMUNOSUPPRESSIVE COMPOUND 2-ACETYL-4-TETRAHYDROXYBUTYL IMIDAZOLEINHIBITS THE ALLOGENEIC MIXED LYMPHOCYTE-REACTION BY SEQUESTRATION OFA RECIRCULATING SUBPOPULATION OF T-CELLS

tyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole(THI) is an immunosuppres sive component of caramel food colouring that causes lymphopenia in mi ce and rats by an unknown mechanism. In this study we investigated som e of the affects of THI on the murine immune system. Initially we show ed that splenic T lymphocytes from mice treated with 50 mg/l THI in th eir drinking water were unable to launch a mixed lymphocyte reaction ( MLR) against allogeneic stimulator cells, and had decreased and delaye d interleukin-2 (IL-2) production. However, these T cells exhibited a normal proliferative response to concanavalin A (Con A), immobilized a nti-CD3 monoclonal antibody (mAb) and anti-CD3 plus anti-CD28 mAb. Fur thermore, the MLR response could be restored by the addition of IL-2 t o the MLR culture. Homing studies using intravenous injection of fluor escence-labelled splenocytes showed that THI treatment decreased absol ute numbers of labelled T and B lymphocytes in the blood and the splee n. Furthermore, these labelled cells reappeared in the blood and the s pleen when mice were taken off THI, indicating that lymphocyte recircu lation and splenic homing were modified reversibly by THI treatment. C essation of THI treatment also resulted in a rapid reappearance of MLR responsiveness in the spleen, indicating that THI treatment does not functionally impair recirculating T cells. Collectively these data are compatible with the concept that a rapidly recirculating population o f T cells, which produce IL-2 in an allogeneic MLR, are lost from the blood and spleen following THI treatment, and are sequestered in other , yet to be identified, tissues.