Mechanism of TCDD-induced suppression of antibody production: effect on T cell-derived cytokine production in the primary immune reaction of mice.
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 microg/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 microg/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.
Ito
Tomohiro
T
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Inouye
Kaoru
K
Fujimaki
Hidekazu
H
Tohyama
Chiharu
C
Nohara
Keiko
K
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D010047:Ovalbumin