Effect of supranutritional maternal and colostral selenium supplementation on passive absorption of immunoglobulin G in selenium-replete dairy calves.

Selenium (Se) is an essential micronutrient for ruminant animals affecting both performance and immune functions. Adding 3 mg of Se/L (in the form of Na selenite) to colostrum has been shown to improve IgG absorption in Se-deficient newborn dairy calves. The objective of our study was to determine the effect of supranutritional maternal and colostral Se supplementation on IgG status of Se-replete dairy calves. The study design was a 2 × 2 × 2 factorial design. During the last 8 wk before calving, dairy cows at a commercial dairy were fed either 0 (control cows) or 105 mg of Se-yeast once weekly (supranutritional Se-yeast-supplemented cows), in addition to Na selenite at 0.3 mg of Se/kg of DM in their ration. After birth, calves were fed pooled colostrum from control or supranutritional Se-yeast-supplemented cows to which 0 or 3 mg of Se/L (in the form of Na selenite) was added. Concentrations of whole-blood (WB) Se and serum Se measured at birth and at 48 h and 14 d of age, and serum IgG concentrations measured at 48 h and 14 and 60 d of age were determined. Calves born to Se-yeast-supplemented cows had higher WB-Se and serum-Se concentrations for the first 2 wk, and higher IgG absorption efficiency (62% at 48 h), resulting in higher serum-IgG concentrations (43% at 48 h and 65% at 14 d) and higher total serum-IgG content (50% at 48 h and 75% at 14 d), compared with calves born to control cows. Calves that received colostrum with added Na selenite had higher WB-Se concentrations for the first 2 wk, but only at 14 d of age were serum-Se concentrations, serum-IgG concentrations (53% higher), and total serum-IgG content (56% higher) higher, compared with calves that were fed colostrum without added Na selenite. Calves born to Se-yeast-supplemented cows that received colostrum from Se-yeast cows without added Na selenite had a higher IgG absorption efficiency compared with all other treatment groups. Our results support that feeding cows supranutritional Se-yeast supplement during the dry period or spiking colostrum with Na selenite both improve IgG status of Se-replete calves.

Reference gene selection for quantitative PCR studies in sheep neutrophils.

Reference genes are essential for studying mRNA expression with quantitative PCR (qPCR). We investigated 11 potential neutrophil reference genes (RPL19, GAPDH, ACTB, B2M, HPRT, G6PD, TFRC, PGK1, YWHAZ, SDHA and GYPC) for sheep under disease conditions of foot rot (FR) and with or without Se supplementation. Initial screening was based on gene expression level (<28 Cq cycles) and variability (SD < 1.5 Cq cycles) and excluded TFRC, GYPC and HPRT from further analysis. Expression stability of the remaining genes was evaluated using four software programs: geNorm, NormFinder, BestKeeper and the comparative delta Cq method. The neutrophil reference genes, G6PD, YWHAZ, GAPDH, RPL19 and SDHA, consistently ranked among the top five most stable genes under these experimental conditions. The SDHA gene expression was not stable in FR-diseased sheep receiving Se treatment and, thus, cannot be recommended as a reference gene. The commonly used genes, PGK1, ACTB and B2M, were not reliable reference genes, underscoring the need to validate neutrophil reference genes under different experimental conditions. Multiple references genes rather than a single gene may provide more robust and reliable results. The best pair of reference genes was SDHA/G6PD in healthy sheep and GADPH/YWHAZ in FR-diseased sheep.

Higher whole-blood selenium is associated with improved immune responses in footrot-affected sheep.

We reported previously that sheep affected with footrot (FR) have lower whole-blood selenium (WB-Se) concentrations and that parenteral Se-supplementation in conjunction with routine control practices accelerates recovery from FR. The purpose of this follow-up study was to investigate the mechanisms by which Se facilitates recovery from FR. Sheep affected with FR (n = 38) were injected monthly for 15 months with either 5 mg Se (FR-Se) or saline (FR-Sal), whereas 19 healthy sheep received no treatment. Adaptive immune function was evaluated after 3 months of Se supplementation by immunizing all sheep with a novel protein, keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity (DTH) skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. Innate immunity was evaluated after 3 months of Se supplementation by measuring intradermal responses to histamine 30 min after injection compared to KLH and saline, and after 15 months of Se supplementation by isolating neutrophils and measuring their bacterial killing ability and relative abundance of mRNA for genes associated with neutrophil migration. Compared to healthy sheep, immune responses to a novel protein were suppressed in FR-affected sheep with smaller decreases in FR-affected sheep that received Se or had WB-Se concentrations above 250 ng/mL at the time of the immune assays. Neutrophil function was suppressed in FR-affected sheep, but was not changed by Se supplementation or WB-Se status. Sheep FR is associated with depressed immune responses to a novel protein, which may be partly restored by improving WB-Se status (> 250 ng/mL).

Functional characterization and gene expression analysis of CD4+ CD25+ regulatory T cells generated in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Although the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are mediated through binding and activation of the aryl hydrocarbon receptor (AhR), the subsequent biochemical and molecular changes that confer immune suppression are not well understood. Mice exposed to TCDD during an acute B6-into-B6D2F1 graft-vs-host response do not develop disease, and recently this has been shown to correlate with the generation of CD4(+) T cells that express CD25 and demonstrate in vitro suppressive function. The purpose of this study was to further characterize these CD4(+) cells (TCDD-CD4(+) cells) by comparing and contrasting them with both natural regulatory CD4(+) T cells (T-regs) and vehicle-treated cells. Cellular anergy, suppressive functions, and cytokine production were examined. We found that TCDD-CD4(+) cells actively proliferate in response to various stimuli but suppress IL-2 production and the proliferation of effector T cells. Like natural T-regs, TCDD-CD4(+) cells do not produce IL-2 and their suppressive function is contact dependent but abrogated by costimulation through glucocorticoid-induced TNFR (GITR). TCDD-CD4(+) cells also secrete significant amounts of IL-10 in response to both polyclonal and alloantigen stimuli. Several genes were significantly up-regulated in TCDD-CD4(+) cells including TGF-beta3, Blimp-1, and granzyme B, as well as genes associated with the IL12-Rb2 signaling pathway. TCDD-CD4(+) cells demonstrated an increased responsiveness to IL-12 as indicated by the phosphorylation levels of STAT4. Only 2% of TCDD-CD4(+) cells express Foxp3, suggesting that the AhR does not rely on Foxp3 for suppressive activity. The generation of CD4(+) cells with regulatory function mediated through activation of the AhR by TCDD may represent a novel pathway for the induction of T-regs.

Effects of feeding pregnant beef cows selenium-enriched alfalfa hay on passive transfer of ovalbumin in their newborn calves.

Intestinal absorption of immunoglobulins is critical for health and survival of newborn calves because there is no transfer of immunoglobulins in utero. The objective of this study was to determine if feeding beef cows Se-enriched alfalfa hay during the last trimester of gestation improves passive transfer of ovalbumin (OVA), a surrogate protein marker for IgG absorption. Control cows (n = 15) were fed non-Se-fortified alfalfa hay (5.3 mg Se/head daily) plus a mineral supplement containing inorganic Se (3 mg Se/head daily). Med-Se (n = 15) and High-Se cows (n = 15) were fed Se-biofortified alfalfa hay (27.6 and 57.5 mg Se/head daily, respectively); both groups received mineral supplement without added Se. Calves were randomly assigned to receive orally administered OVA at 12, 24, or 36 h of age. Calves that received their oral dose of OVA at 12 h of age had higher serum OVA concentrations across the first 48 h of life if born to High-Se cows compared to calves born to Control cows (P = 0.05), with intermediate values for calves born to Med-Se cows. Our results, using OVA as a model for passive transfer, suggest that if calves do not receive adequate colostrum to reach maximum pinocytosis, then supranutritional Se supplementation in beef cattle may improve passive transfer in their calves, if calves receive colostrum within the first 12 h of age.

Dietary Enrichment with 20% Fish Oil Decreases Mucus Production and the Inflammatory Response in Mice with Ovalbumin-Induced Allergic Lung Inflammation.

The prevalence of asthma has increased in recent decades, which may be related to higher dietary intake of (n-6) polyunsaturated fatty acids (PUFA) and lower intake of (n-3) PUFA, e.g., those contained in fish oil. The objective of this study was to determine if dietary PUFA enrichment decreases mucus production or the inflammatory response associated with ovalbumin (OVA)-induced allergic lung inflammation. Mice (n = 10/group) were fed control, 20% fish oil, or 20% corn oil enriched diets for a total of 12 weeks. At 8 and 10 weeks, mice were given an intraperitoneal injection of saline (10 control-fed mice) or OVA (30 remaining mice). Once at 10 weeks and on 3 consecutive days during week 12, mice were challenged by nebulizing with saline or OVA. Mice were euthanized 24 hours after the last challenge and blood was collected for plasma FA analysis. Bronchoalveolar lavage (BAL) fluid was collected to determine cell composition and Th2-type cytokine (IL-4, IL-13) concentrations. Periodic acid-Schiff (PAS) + mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue were quantified using morphometric analysis. Relative abundance of mRNA for mucin (Muc4, Muc5ac, and Muc5b) and Th2-type cytokine (IL-4, IL-5, and IL-13) genes were compared with ß-actin by qPCR. Supplementation with either corn oil or fish oil effectively altered plasma FA profiles towards more (n-6) FA or (n-3) FA, respectively (P < 0.0001). Sensitization and challenge with OVA increased the proportion of neutrophils, lymphocytes, and eosinophils, and decreased the proportion of macrophages and concentrations of IL-13 in BAL fluid; increased the percentage of PAS+ mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue; and increased gene expression of mucins (Muc4, Muc5ac, and Muc5b) and Th2-type cytokines (IL-5 and IL-13) in lung tissue of control-fed mice. Dietary PUFA reversed the increase in PAS+ mucus-producing cells (P = 0.003). In addition, dietary enrichment with fish oil attenuated the percentage of CD45+ inflammatory cell infiltrates in lung tissue, and increased Muc4 and Muc 5b gene expression compared with OVA-sensitized and challenged control mice. In conclusion, dietary enrichment with either (n-3) or (n-6) PUFA decreased mucus production in lung tissues of OVA-sensitized and challenged mice. More specifically, enrichment with dietary (n-3) PUFA decreased CD45+ inflammatory cell infiltrates, thus inducing potentially beneficial changes in lung tissue of OVA-sensitized and challenged mice.

Effect of selenium yeast supplementation on naturally acquired parasitic infection in ewes.

Gastrointestinal parasites cause substantial economic losses in pasture-based sheep production systems. Supranutritional organic selenium (Se) supplementation may be beneficial because it improves immune responses to pathogens. To evaluate the effect of Se-yeast supplementation on gastrointestinal parasite load, 30 ewes per treatment group were drenched weekly with no Se, 4.9 mg Se/week as Se yeast (maximum FDA-allowed concentration), or supranutritional concentrations of Se yeast (14.7 and 24.5 mg Se/week) starting early fall for 85 weeks. Fecal samples were collected at weeks 63, 66, 78, and 84 and counted for total trichostrongyle-type eggs and Haemonchus contortus eggs (in samples with ≥200 trichostrongyle eggs/g feces). During breeding season (fall), ewes were kept on pasture; ewes receiving 24.5 mg Se/week had lower fecal trichostrongyle egg counts (93 ± 40 eggs/g feces) compared with ewes receiving no Se (537 ± 257 eggs/g feces; P = 0.007) or ewes receiving 4.9 mg Se/week as Se yeast (398 ± 208 eggs/g feces; P = 0.03). In winter, fecal trichostrongyle egg counts decreased, and group differences were not apparent. During lambing season (spring), ewes were kept in the barn and fecal trichostrongyle egg counts increased, although no group differences were observed. However, none of the ewes receiving supranutritional Se yeast, and with trichostrongyle egg counts ≥200 eggs/g of feces, but four of the ewes receiving lower Se dosages had H. contortus egg counts ≥1,000 eggs/g feces (P = 0.04). Our results suggest that supranutritional Se-yeast supplementation may enhance resistance to naturally occurring H. contortus gastrointestinal parasitism in sheep.

Effect of supranutritional organic selenium supplementation on postpartum blood micronutrients, antioxidants, metabolites, and inflammation biomarkers in selenium-replete dairy cows.

Dairy cows have increased nutritional requirements for antioxidants postpartum. Supranutritional organic Se supplementation may be beneficial because selenoproteins are involved in regulating oxidative stress and inflammation. Our objective was to determine whether feeding Se-yeast above requirements to Se-replete dairy cows during late gestation affects blood micronutrients, antioxidants, metabolites, and inflammation biomarkers postpartum. During the last 8-weeks before calving, dairy cows at a commercial farm were fed either 0 (control) or 105 mg Se-yeast once weekly (supranutritional Se-yeast), in addition to Na selenite at 0.3 mg Se/kg dry matter in their rations. Concentrations of whole-blood (WB) Se and serum Se, erythrocyte glutathione (GSH), and serum albumin, cholesterol, α-tocopherol, haptoglobin, serum amyloid A (SAA), calcium, magnesium, phosphorus, non-esterified fatty acids, and ß-hydroxybutyrate were measured directly after calving, at 48 h, and 14 days of lactation in 10 cows of each group. Supranutritional Se-yeast supplementation affected indicators of antioxidant status and inflammation. Cows fed a supranutritional Se-yeast supplement during the last 8-weeks of gestation had higher Se concentrations in WB (overall 52 % higher) and serum (overall 36 % higher) at all-time points, had higher SAA concentrations at 48 h (98 % higher), had higher erythrocyte GSH (38 % higher) and serum albumin concentrations (6.6 % higher) at 14 days, and had lower serum cholesterol concentrations and higher α-tocopherol/cholesterol ratios at calving and at 48 h compared with control cows. In conclusion, feeding Se-replete cows during late gestation a supranutritional Se-yeast supplement improves antioxidant status and immune responses after calving without negatively impacting other micronutrients and energy status.

Effects of feeding selenium-enriched alfalfa hay on immunity and health of weaned beef calves.

Previously, we reported that feeding selenium (Se)-enriched forage improves antibody titers in mature beef cows, and whole-blood Se concentrations and growth rates in weaned beef calves. Our current objective was to test whether beef calves fed Se-enriched alfalfa hay during the transition period between weaning and movement to a feedlot also have improved immune responses and slaughter weights. Recently weaned beef calves (n = 60) were fed an alfalfa-hay-based diet for 7 weeks, which was harvested from fields fertilized with sodium selenate at 0, 22.5, 45.0, or 89.9 g Se/ha. All calves were immunized with J-5 Escherichia coli bacterin. Serum was collected for antibody titers 2 weeks after the third immunization. Whole-blood neutrophils collected at 6 or 7 weeks were evaluated for total antioxidant potential, bacterial killing activity, and expression of genes associated with selenoproteins and innate immunity. Calves fed the highest versus the lowest level of Se-enriched alfalfa hay had higher antibody titers (P = 0.02), thioredoxin reductase-2 mRNA levels (P = 0.07), and a greater neutrophil total antioxidant potential (P = 0.10), whereas mRNA levels of interleukin-8 receptor (P = 0.02), L-selectin (P = 0.07), and thioredoxin reductase-1 (P = 0.07) were lower. In the feedlot, calves previously fed the highest-Se forage had lower mortality (P = 0.04) and greater slaughter weights (P = 0.02). Our results suggest that, in areas with low-forage Se concentrations, feeding beef calves Se-enriched alfalfa hay during the weaning transition period improves vaccination responses and subsequent growth and survival in the feedlot.

Selenium supplementation alters gene expression profiles associated with innate immunity in whole-blood neutrophils of sheep.

Footrot (FR) is a common, contagious bacterial disease of sheep that results in lameness and significant economic losses for producers. We previously reported that sheep affected with FR have lower whole-blood (WB) selenium (Se) concentrations and that Se supplementation in conjunction with routine control practices accelerates recovery from FR. To determine whether oral Se-yeast administered at supranutritional levels (>4.9 mg Se/week) alters the ability of sheep to resist or recover from FR infection, 60 ewes with and 60 ewes without FR were drenched once weekly for 62.5 weeks with 0, 4.9, 14.7, or 24.5 mg organic Se-yeast (30 ewes per treatment group). Footrot prevalence and severity were measured at 0, 20, 28, 40, and 60 weeks of Se supplementation. Genomic expression of eight WB-neutrophil genes for selenoproteins and seven WB-neutrophil genes for proteins involved in innate immunity was determined at the end of the treatment period using SYBR Green and quantitative polymerase chain reaction methodology. Supranutritional Se-yeast supplementation successfully increased Se status in sheep but did not prevent FR. Supranutritional Se-yeast supplementation increased WB-neutrophil expression of genes involved in innate immunity: L-selectin, interleukin-8 receptor, and toll-like receptor 4, which were or tended to be lower in ewes affected with FR. Furthermore, supranutritional Se-yeast supplementation altered the expression of selenoprotein genes involved in innate immunity, increasing selenoprotein S and glutathione peroxidase 4 and decreasing iodothyronine deiodinases 2 and 3. In conclusion, supranutritional Se-yeast supplementation does not prevent FR, but does alter WB-neutrophil gene expression profiles associated with innate immunity, including reversing those impacted by FR.

Selenium supplementation restores innate and humoral immune responses in footrot-affected sheep.

Dietary selenium (Se) alters whole-blood Se concentrations in sheep, dependent upon Se source and dosage administered, but little is known about effects on immune function. We used footrot (FR) as a disease model to test the effects of supranutritional Se supplementation on immune function. To determine the effect of Se-source (organic Se-yeast, inorganic Na-selenite or Na-selenate) and Se-dosage (1, 3, 5 times FDA-permitted level) on FR severity, 120 ewes with and 120 ewes without FR were drenched weekly for 62 weeks with different Se sources and dosages (30 ewes/treatment group). Innate immunity was evaluated after 62 weeks of supplementation by measuring neutrophil bacterial killing ability. Adaptive immune function was evaluated by immunizing sheep with keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. At baseline, FR-affected ewes had lower whole-blood and serum-Se concentrations; this difference was not observed after Se supplementation. Se supplementation increased neutrophil bacterial killing percentages in FR-affected sheep to percentages observed in supplemented and non-supplemented healthy sheep. Similarly, Se supplementation increased KLH antibody titers in FR-affected sheep to titers observed in healthy sheep. FR-affected sheep demonstrated suppressed cell-mediated immunity at 24 hours after intradermal KLH challenge, although there was no improvement with Se supplementation. We did not consistently prevent nor improve recovery from FR over the 62 week Se-treatment period. In conclusion, Se supplementation does not prevent FR, but does restore innate and humoral immune functions negatively affected by FR.

Effect of feeding selenium-fertilized alfalfa hay on performance of weaned beef calves.

Selenium (Se) is an essential micronutrient in cattle, and Se-deficiency can affect morbidity and mortality. Calves may have greater Se requirements during periods of stress, such as during the transitional period between weaning and movement to a feedlot. Previously, we showed that feeding Se-fertilized forage increases whole-blood (WB) Se concentrations in mature beef cows. Our current objective was to test whether feeding Se-fertilized forage increases WB-Se concentrations and performance in weaned beef calves. Recently weaned beef calves (n = 60) were blocked by body weight, randomly assigned to 4 groups, and fed an alfalfa hay based diet for 7 wk, which was harvested from fields fertilized with sodium-selenate at a rate of 0, 22.5, 45.0, or 89.9 g Se/ha. Blood samples were collected weekly and analyzed for WB-Se concentrations. Body weight and health status of calves were monitored during the 7-wk feeding trial. Increasing application rates of Se fertilizer resulted in increased alfalfa hay Se content for that cutting of alfalfa (0.07, 0.95, 1.55, 3.26 mg Se/kg dry matter for Se application rates of 0, 22.5, 45.0, or 89.9 g Se/ha, respectively). Feeding Se-fertilized alfalfa hay during the 7-wk preconditioning period increased WB-Se concentrations (P Linear<0.001) and body weights (P Linear = 0.002) depending upon the Se-application rate. Based upon our results we suggest that soil-Se fertilization is a potential management tool to improve Se-status and performance in weaned calves in areas with low soil-Se concentrations.

Influence of dietary antioxidants and fatty acids on neutrophil mediated bacterial killing and gene expression in healthy Beagles.

Dietary (n-3) fatty acids from fish oil have been used to modulate immune function in many mammalian species. Together, dietary antioxidants and behavioral enrichment have been shown to enhance neutrophil phagocytosis in geriatric Beagle dogs. The purpose of this study was to further investigate the effects of vitamins E and C, in combination with dietary fish oil, on neutrophil mediated bacterial killing, and on transcript levels of selected neutrophil mRNA. Fifty adult Beagle dogs were randomized into five dietary treatment groups for 60 days. All foods were complete and balanced and met the nutrient profiles of AAFCO for adult dogs. For 60 days before study initiation, dogs consumed a pretrial food that contained 74 IU/kg vitamin E and 0 mg/kg vitamin C. The five experimental foods were confirmed by analytical methods to contain ≥640 IU/kg vitamin E and 130 mg/kg vitamin C (as fed). Experimental foods ranged from low levels of EPA and DHA (pretrial food and lowest experimental food had 0.01% EPA and no detectable DHA) to the highest experimental food with 0.25% EPA and 0.17% DHA. Ex vivo bactericidal activity of activated, peripheral-blood neutrophils against Lactococcus lactis was determined after 1 h incubation. Bactericidal activity was calculated as a percentage of control values (bacteria incubated in media without neutrophils). Transcript levels of genes involved in neutrophil-mediated immune functions were determined by real-time qPCR. Dogs in all treatment groups had increased serum vitamin E concentration (P<0.01). After consuming experimental food for 60 days, neutrophils from dogs in all 5 treatment groups also had increased bactericidal activity (P<0.01). Dietary fish oil however, had no effect on bactericidal activity. Stepwise multiple regression analysis demonstrated that the change in neutrophil mediated bacterial killing was significantly correlated to changes in gene expression of interleukin-8 receptor (IL-8R), interleukin converting enzyme (ICE), and myeloperoxidase (MPO; r(2)=0.33; P=0.003). When stepwise multiple regression analysis was performed considering each mRNA as a dependent variable and change in selected individual and summed fatty acid concentrations as independent variables, change in the ratio of saturated fatty acids (SFA) to polyunsaturated fatty acids (PUFA) was significant (P≤0.05) in the mRNA regression analyses for IL-8R, ICE, MPO, and cyclooxygenase-2. In summary, circulating neutrophils from dogs fed diets enriched in vitamins E and C had significantly increased bactericidal activity as well as altered gene expression. Change in SFA to PUFA ratio also altered neutrophil gene expression.

Aged Beagle dogs have decreased neutrophil phagocytosis and neutrophil-related gene expression compared to younger dogs.

Information on aging and the innate immune response in dogs is needed in order to understand the impact of age on the innate immune system and to design diets that might improve age-associated changes in innate immunity. The purpose of this study was to investigate the effects of age on phagocytosis and antibacterial activity of peripheral blood neutrophils, and on expression levels of selected mRNA specific for neutrophil migration or killing functions. Three groups of Beagle dogs were evaluated in a cross-sectional study design: puppies less than 1 year of age (n=15), adults 1-7 years of age (n=37) and senior adults over 8 years of age (n=25). Neutrophil phagocytosis and killing of Lactococcus lactis were assessed, and the relative abundance of mRNAs for myeloperoxidase (MPO), l-selectin, interleukin-8 receptor (IL-8R) and interleukin-1beta-converting enzyme (ICE) was determined. Results showed that in Beagle dogs there is a significant effect of age on percent bacterial killing by neutrophils. Average decline in phagocytic ability at 4 and 10 years of age (compared to 1 year of age) was 25% and 39%, respectively. In addition, younger dogs have significantly higher levels of mRNA for IL-8R, l-selectin and ICE. These results suggest that older dogs have depressed innate immune responses compared with younger dogs, which may contribute to increased morbidity and mortality with aging.

Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes.

The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), is a novel inducer of adaptive Tregs. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent AHR ligand, induces adaptive CD4+CD25+ Tregs during an acute graft-versus-host (GvH) response and prevents the generation of allospecific cytotoxic T lymphocytes. TCDD also suppresses the induction of experimental autoimmune encephalitis in association with an expanded population of Foxp3+ Tregs. In this study, we show that chronic treatment of NOD mice with TCDD potently suppresses the development of autoimmune Type 1 diabetes in parallel with greatly reduced pancreatic islet insulitis and an expanded population of CD4+CD25+Foxp3+ cells in the pancreatic lymph nodes. When treatment with TCDD was terminated after 15 weeks (23 weeks of age), mice developed diabetes over the next 8 weeks in association with lower numbers of Tregs and decreased activation of AHR. Analysis of the expression levels of several genes associated with inflammation, T-cell activation and/or Treg function in pancreatic lymph node cells failed to reveal any differences associated with TCDD treatment. Taken together, the data suggest that AHR activation by TCDD-like ligands may represent a novel avenue for treatment of immune-mediated diseases.