Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine production in ovalbumin (OVA)-immunized C57Bl/6 mice

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress both cellular and humoral immunity. Effector T cell-derived type-2 cytokines. including IL-4 and IL-5, play pivotal roles in humoral immunity. Herein, we studied whether TCDD affects type-2 cytokine productions during the immune response. C57B1/6 mice were intraperitoneally immunized with ovalbumin (OVA) and orally administered 5 or 20 mug TCDD/kg on Day 0, and then challenged with OVA on Day 21. Seven days later (Day 28), antigen-specific antibodies in plasma, and T cell-derived cytokines produced by splenocytes and proliferation of splenocytes upon ex vivo re-stimulation with OVA were investigated, The quantities of IgM class and IgG1 class OVA-specific antibodies in plasma were reduced by 5 or 20 mug TCDD/kg and by 20 mug TCDD/kg, respectively. While thymus weight and cellularity were reduced by 20 mug TCDD/kg, spleen weight and cellularity were not changed by either 5 or 20 mug TCDD/kg. The proportions of B and T cells in the spleen were not affected by TCDD exposure. On the other hand. splenocytes from mice treated with 5 or 20 mug TCDD/kg were shown to produce less IL-4 or IL-5 upon ex vivo re-stimulation with OVA. Production of the T cell growth factor IL-2 was also decreased in splenocytes from TCDD-treated mice. In contrast. the type-1 cytokine IFN-gamma was increased by TCDD. Twenty micrograms of TCDD/kg suppressed OVA- or T cell mitogen (Con A)-stimulated proliferation of splenocytes, but did not affect B cell mitogen (LPS)-stimulated proliferation. These results suggested compromised T cell activation and suppressed type-2 cytokine production by T cells to be involved in the impaired humoral immunity associated with TCDD exposure. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.