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 factor 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 reports 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 compromised, however, their functional immune response has not been directly tested. In the studies presented here, we examined the immune response of two strains of 8- to 10-week-old AhR-deficient mice. Mice were challenged with model antigens, allogeneic P815 tumor cells, or sheep red blood cells, and their ability to generate cell-mediated and humoral immune responses was examined. In addition, to address the obligatory role of the AhR in TCDD-induced immune suppression, we examined the immune response of the AhR-null animals following exposure to an immunosuppressive dose of TCDD. Results from these studies showed that AhR-deficient mice were able to mount normal productive immune responses to both 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 these studies suggest that the absence of the AhR does not impact the function of the immune system, but confirm the findings of previous studies that have indicated the AhR plays an obligatory role in TCDD-induced immune suppression.
Vorderstrasse
B A
BA
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, USA.
Steppan
L B
LB
Silverstone
A E
AE
Kerkvliet
N I
NI
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000276:immunology; D004351:Drug Resistance; D004912:Erythrocytes / Q000276:immunology; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency* / Q000235:genetics; D012756:Sheep; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007166:Immunosuppressive Agents; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon