Evaluation of the effect of low-level 2,3,7,8-tetrachlorodibenzo- p-dioxin exposure on cell mediated immunity

Abstract

The immunotoxicity of TCDD in the mouse has been well documented. To date, the most sensitive endpoint to TCDD-induced toxicity in mice is that reported by Clark et al. (Clark, D.A., Gauldie, J., Szewczuk M.R. and Sweeney, G. (1981) Proc. Soc. Exper. Biol. Med. 168, 290.) who found that TCDD suppressed the murine cytotoxic T lymphocyte (CTL) response following four weekly doses of 4 ng TCDD/kg/week. However, these results have never been corroborated, as other laboratories have been unable to detect immunosuppression by TCDD at such low levels. In this study, we evaluated the effect of TCDD on the in vivo- and in vitro- generated CTL response to P815 mastocytoma cells in adult C57BL/6J female mice via a 51Cr release assay. Mice were given weekly intraperitoneal injections of TCDD or vehicle for 4 weeks at dosages ranging from 0.01 to 3.00 μg/kg/week. No statistically significant suppression of the in vivo- or in vitro-generated CTL response was detected at any dosage. As expected, significant increases in liver weights and decreases in thymus weights were observed at TCDD dosages of 1.0 and 3.0 μg/kg/week. Likewise, suppression of the antibody plaque forming cell response to sheep erythrocytes was observed at dosages of 1.0 and 3.0 μg TCDD/kg/week. Although expected humoral immunosuppression and organ effects were observed, our data do not support suppression of murine CTL responses at the TCDD doses employed in this study.