Objective To elucidate the role of APC in the Tk-induced
suppression by using animal experimental system. Methods Dose-dependent
curves of Tk-induced inhibition of
lymphoproliferation to soluble Ag OVA, mitogen ConA, and anti-CD3/CD28 McAbs were determined by in vitro assay. T cells from lymph node of C57BL/6 mice immunized with OVA were subjected to repeat stimulation with OVA to establish OVA-specific T cell lines(Tova). The IL-2-stimulated lymphoproliferation of the mixed T cell line was further examined as a test system to reveal the effect of Tk on the T cells. The possible apoptosis of the splenic mononuclear cells (SMC) induced by Tk was detected by FACS. Furthermore, bone marrow-derived dendritic cells (BDCs) pulse-treated with or without Tk (100 ng/ml) for 12 h were assayed for their APC capabilities of activating Tova. Results Tk of low doses from 1 ng/ml to 500 ng/ml suppressed the lymphoproliferation stimulated by OVA and by ConA. However there was little
suppression for IL-2 or for anti-CD3/CD28 McAb-induced lymphoproliferation. Tk did not cause apoptosis of SMC at the concentration less than 5 ng/ml in our experiment. As compared with the control, the lymphoproliferation of Tova to the OVA-pulsed BDCs was remarkably depressed in the presence of Tk. In contrast, the proliferation was not affected when purified Tova was pulsed with Tk alone. Conclusion Tk is active in exerting its effects on APCs for inducing suppression of T responses.