T cell-derived IL-5 production is a sensitive target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
The immune system is one of the organs most vulnerable to the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Among the various immunotoxic effects of TCDD, the thymus involution and suppression of IgM antibody production are well known sensitive reactions of the thymocytes and B cells affected by TCDD. Recently, we reported that TCDD greatly inhibits the production of type-2 helper T (Th2) cell-derived cytokines, especially IL-5, by the splenocytes in mice immunized with ovalbumin (OVA). In the present study, we investigated the dose-dependency of these TCDD immunotoxic effects in OVA-immunized mice to identify the most sensitive target. Mice of two age groups, 6 weeks old and 3 weeks old, were dosed with 0.3, 1.0, or 3.0 microg TCDD/kg and immunized with OVA using alum as an adjuvant. Seven days later, the thymus weight, thymocyte population, antigen-specific IgM in the plasma, and IL-5 production by the splenocytes were examined. Among them, IL-5 production was significantly suppressed by all three doses of TCDD and reduced to about 30% by even a small dose of 0.3 microg TCDD/kg in both age groups. The thymus weight was significantly reduced by 1.0 microg or 3.0 microg TCDD/kg, but IgM production was not affected by up to 3.0 microg/kg of TCDD in both age groups. Taken together, the Th2 cell-derived IL-5 production was the most sensitive endpoint detecting TCDD toxicity among those examined. Our results also suggest that effector T cells are targets more vulnerable to TCDD toxicity than thymocytes or antibody-producing B cells in the OVA-immunized mice.
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Kaoru
K
Inouye
Xiaoqing
X
Pan
Noritaka
N
Imai
Tomohiro
T
Ito
Teiji
T
Takei
Chiharu
C
Tohyama
Keiko
K
Nohara
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007075:Immunoglobulin M / Q000097:blood; D015848:Interleukin-5 / Q000276:immunology*; D007774:Lactation; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D014886:Weaning
D007075:Immunoglobulin M; D015848:Interleukin-5; D000072317:Polychlorinated Dibenzodioxins; D010047:Ovalbumin