T HELPER CELL UNRESPONSIVENESS INDUCED BY SUPPRESSOR T CELLS.
AI Colovai, R Ciubotariu, Z Liu, J Li, S. Jiang and N Suciu-Foca, Department of Pathology, Columbia University, New York, NY.
Recent data indicate that human suppressor T cells (Ts) can be educated ex-vivo by multiple antigenic stimulation of CD8+CD28- T cells. Ts which inhibit both the direct and indirect recognition pathway have been described. To investigate the mechanism underlying Ts-mediated suppression, we have tested the effect of Ts on activation events which occur upon stimulation of Th cells with xenogeneic APC. We found that Ts inhibited the expression of CD86 on the surface of stimulating APC and the upregulation of CD40L on the surface of Th. Ts drastically reduced Th capacity to produce IL-2, while the expression of IL-2 receptor (CD25) on the surface of Th was not affected. Th reactivity could be restored by adding to the cultures exogenous IL-2 or anti-CD28 mAb, indicating that Th unresponsiveness induced by Ts is probably caused by anergy. Ts-mediated suppression could not be circumvented by the addition to the cultures of PMA, which activates protein kinase C, and/or ionomycin, which activates intracellular calcium, indicating that Ts interfere with distinct signal transduction pathway(s). These findings indicate that ex-vivo educated Ts may provide a useful tool for down-regulation of cellular reactivity to xenografts.