Toxicological Sciences 70, 46-54 (2002)
Copyright © 2002 by the Society of Toxicology
IMMUNOTOXICOLOGY |
Mechanism of TCDD-Induced Suppression of Antibody Production: Effect on T Cell-Derived Cytokine Production in the Primary Immune Reaction of Mice
,1
* Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan;
CREST, JST (Japan Science and Technology), Kawaguchi 332-0012, Japan; and
Japan Society for the Promotion of Science (JSPS), Tokyo 102-8471, Japan
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress antigen-specific antibody production in humoral immune reactions, but the precise mechanism remains unclear. Since T cell activation and subsequent production of type 2 helper T (Th2) cell-derived cytokines are required for antigen-specific antibody production in humoral immunity, we examined the effects of TCDD on splenic T cell numbers, T cell growth factor IL-2 production, and Th2 cell-derived cytokine production. C57BL/6N mice were orally given TCDD (20 µg/kg) or vehicle, and immediately intraperitoneally immunized with ovalbumin (OVA) adsorbed to alum, and cellular changes in the spleen and cytokine production by spleen cells were investigated from Day 1 to Day 14. In vehicle-control mice the numbers of splenic CD3+ T cells increased from Day 7 onward, but no increase was observed in the TCDD-exposed mice. When spleen cells from control mice were cultured and restimulated with OVA ex vivo, a significant amount of IL-2 was found from Day 1, but it decreased on Day 7, whereas TCDD exposure promptly suppressed the increase on Day 4. TCDD exposure significantly suppressed the production of Th2 cell-derived cytokines IL-4, IL-5, and IL-6, which were prominently increased from Day 4 onward in control mice. The dose-dependent study showed that IL-5 production was significantly suppressed in a dose-dependent manner starting at 1 µg/kg TCDD. Moreover, separation and reconstitution studies showed that the TCDD-induced suppression of IL-5 production was due to the impaired function of T cells rather than that of antigen-presenting cells. The results of this study suggest that TCDD-induced suppression of T cell activation and Th2-type cytokine production is involved in the impairment of antigen-specific antibody production.
Key Words: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; Th2 cell-derived cytokine; T cell growth factor; antibody production; primary immune reaction.
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