title: Suppression of cytotoxic T lymphocyte activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin occurs in vivo, but not in vitro, and is independent of corticosterone elevation.
abstract: Previous studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent immunosuppressive compound. In our laboratory, TCDD and structurally related polychlorinated biphenyls (PCBs) have been shown to suppress alloantigen-specific cytotoxic T lymphocyte (CTL) activity in C57B1/6 mice. PCB-induced CTL suppression occurs coincident with significant elevation of plasma glucocorticoid (GC) levels (> 500 ng/ml). Since GC elevation can cause immune suppression, this study was conducted to determine if TCDD-induced CTL suppression is correlated with elevation of plasma corticosterone (CS), the major GC in mice. Single oral doses of TCDD (2.5-40 micrograms/kg) induced a dose-dependent suppression of CTL activity with a calculated 50% immunosuppressive dose (ID50) occurring at 7.2 micrograms/kg. When total lytic units (LU)/spleen were calculated, the ID50 was 2.8 micrograms/kg. In contrast, plasma CS levels were not significantly altered at doses below 40 micrograms/kg. These data suggest that TCDD-induced CTL suppression is not dependent on CS elevation. The direct effect of TCDD on CTL generation was tested by adding TCDD at 10(-13)-10(-9) M to in vitro mixed lymphocyte-tumor cell (MLTC) cultures. No alteration of CTL activity was observed after 5 days of culture at any TCDD concentration. In contrast, CS alone significantly suppressed CTL activity in vitro. CS-induced CTL suppression in vitro was neither enhanced nor inhibited by the presence of TCDD. These results suggest that TCDD causes CTL suppression in vivo by a mechanism that does not involve CS.
authors.affiliation: Department of Agricultural Chemistry, Oregon State University, Corvallis 97331, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: De Krey
authors.forename: N I
authors.initials: NI
authors.lastname: Kerkvliet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D003345:Corticosterone