EVALUATION OF THE EFFECT OF LOW-LEVEL 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN EXPOSURE ON CELL-MEDIATED-IMMUNITY

The immunotoxicity of TCDD in the mouse has been well documented. To d ate, the most sensitive endpoint to TCDD-induced toxicity in mice is t hat reported by Clark et al. (Clark, D.A., Gauldie, J., Szewczuk M.R. and Sweeney, G. (1981) Proc, Sec, Exper. Biol. Med. 168, 290.) who fou nd that TCDD suppressed the murine cytotoxic T lymphocyte (CTL) respon se following four weekly doses of 4 ng TCDD/kg/week. However, these re sults have never been corroborated, as other laboratories have been un able to detect immunosuppression by TCDD at such low levels. In this s tudy, we evaluated the effect of TCDD on the in vivo- and in vitro-gen erated CTL response to P815 mastocytoma cells in adult C57BL/6J female mice via a Cr-51 release assay. Mice were given weekly intraperitonea l injections of TCDD or vehicle for 4 weeks at dosages ranging from 0. 01 to 3.00 mu g/kg/week. No statistically significant suppression of t he in vivo- or in vitro-generated CTL response was detected at any dos age. As expected, significant increases in liver weights and decreases in thymus weights were observed at TCDD dosages of 1.0 and 3.0 mu g/k g/week. Likewise, suppression of the antibody plaque-forming cell resp onse to sheep erythrocytes was observed at dosages of 1.0 and 3.0 mu g TCDD/kg/week. Although expected humoral immunosuppression and organ e ffects were observed, our data do not support suppression of murine CT L responses at the TCDD doses employed in this study.