Aryl hydrocarbon receptor-deficient mice generate normal immune responses to model antigens and are resistant to TCDD-induced immune suppression

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription fac tor that mediates many of the toxic effects induced by exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), a high-affinity AhR ligand and a potent immunotoxicant. AhR-deficient mice have been constructed, and there are re ports that the animals display altered splenic architecture and cellularity with an apparent increased incidence of infection. These observations have led to speculation that the immune system of these animals might be compro mised, however, their functional immune response has not been directly test ed. In the studies presented here, we examined the immune response of two s trains of 8- to 10-week-old AhR-deficient mice. Mice were challenged with m odel antigens, allogeneic P815 tumor cells, or sheep red blood cells, and t heir ability to generate cell-mediated and humoral immune responses was exa mined. In addition, to address the obligatory role of the AhR in TCDD-induc ed immune suppression, we examined the immune response of the AhR-null anim als following exposure to an immunosuppressive dose of TCDD. Results from t hese studies showed that AhR-deficient mice were able to mount normal produ ctive immune responses to bath model antigens and that neither the cellular nor the humoral response was suppressed by exposure to TCDD. Interestingly , however, we found that the immune response of heterozygous AhR(+/-) mice was less sensitive to TCDD than homozygous AhR(+/+) mice. The results of th ese studies suggest that the absence of the AhR does not impact the functio n of the immune system, but confirm the findings of previous studies that h ave indicated the AhR plays an obligatory role in TCDD-induced immune suppr ession. (C) 2001 Academic Press.