DIRECT EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON HUMANTONSILLAR LYMPHOCYTES

Murine lymphocyte function is quite sensitive to TCDD. However, in con trast to the murine model, the corresponding functional studies have n ot been undertaken with human lymphocytes. One laboratory has recently demonstrated that human tonsillar lymphocytes (HTL) possess the aryl hydrocarbon (Ah) receptor which mediates many of the effects of TCDD. This observation suggested that HTL may be sensitive to TCDD. In mitog en stimulated HTL, TCDD induced a dose-dependent increase in 7-ethoxyr esorufin-O-deethylase (EROD) synthesis. Because we recently demonstrat ed that background proliferation in HTL and murine splenocytes was sup pressed by TCDD, we purified human and murine B-cells into high densit y and low density populations. In low density human B-cells, TCDD supp ressed background proliferation and IgM secretion from 0.3 to 30 nM. I nterestingly, TCDD produced comparable effects on background prolifera tion and IgM secretion in purified low density murine B-cells. When lo w density human B-cells were stimulated with LPS and TRF, TCDD suppres sed both proliferation and IgG secretion in a dose-dependent manner fr om 0.3 to 30 nM, although the suppression was modest when compared to the magnitude of suppression of the background responses. In contrast, TCDD did not alter background or stimulated proliferation in high den sity human B-cells. These results indicate that TCDD has a direct effe ct on human tonsillar lymphocyte activity and suggest that low density B-cells are a sensitive cellular target.