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

Nohara, Keiko; Fujimaki, Hidekazu; Tsukumo, Shin Ichi; Inouye, Kaoru; Sone, Hirohito; Tohyama, Chiharu

doi:10.1016/s0300-483x(01)00582-0

Cited by 59 publications

(34 citation statements)

References 34 publications

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“…Numerous experimental studies showed that TCDD may suppress both humoral and cell-mediated immune responses (Birnbaum and Tuomisto 2000;Kerkvliet 2002). Inhibition of immunoglobulin secretion has been demonstrated in multiple animal species (Birnbaum and Tuomisto 2000;Nohara et al 2002;Vorderstrasse et al 2001), as well as in human lymphocytes cultivated in vitro (Sulentic et al 2000). Zober et al (1994) found an increased incidence of infectious and parasitic diseases in a small retrospective cohort study of TCDD-exposed workers, but clinical diagnoses were ill-defined.…”

Section: Discussionmentioning

confidence: 99%

“…The immune system is one of its most sensitive targets (Birnbaum and Tuomisto 2000). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals (Birnbaum and Tuomisto 2000;Holsapple et al 1991;Nohara et al 2002). In humans, increased incidence of and mortality from lymphatic tumors have been found in exposed subjects, even though there is a lack of consistency among studies (Bertazzi et al 2001;IARC 1997).…”

mentioning

confidence: 99%

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Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Baccarelli

Mocarelli

Patterson

et al. 2002

Environ Health Perspect

119

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Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Baccarelli

Mocarelli

Patterson

et al. 2002

Environ Health Perspect

119

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“…Spleen cells and bone marrow cells prepared from thigh bones were treated with ammonium chroride/EDTA solution (0.83% NH 4 Cl, 0.1% KHCO 3 , 0.37% EDTA (pH 7.4)) for 2 min at room temperature to eliminate RBCs and then were washed with PBS (33). Cells were counted with a hemocytometer after staining with trypan blue.…”

Section: Cell Preparationmentioning

confidence: 99%

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Nohara

Pan

Tsukumo

et al. 2005

The Journal of Immunology

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The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix-PER-ARNT-SIM superfamily. Xenobiotics, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, bind the receptor and trigger diverse biological reactions. Thymocyte development and T cell-dependent immune reactions are sensitive targets of AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity. However, the exact role of the AhR in T cells in animals exposed to exogenous ligands has not been clarified because indirect effects of activated AhR in other cell types cannot be excluded. In this study, we generated transgenic (Tg) mice expressing a constitutively active mutant of AhR under the regulation of a T cell-specific CD2 promoter to examine AhR function in T cells. The mRNAs of the constitutively active mutant of AhR and an AhR-induced gene, CYP1A1, were expressed in the thymus and spleen of the Tg mice. The transgene expression was clearly detected in the thymocytes, CD4, and CD8 T cells, but not in the B cells or thymus stromal cells. These Tg mice had a decreased number of thymocytes and an increased percentage of CD8 single-positive thymocytes, but their splenocytes were much less affected. By contrast, the increase in number of T cells and B cells taking place in the spleen after immunization was significantly suppressed in the Tg mice. These results clearly show that AhR activation in the T-lineage cells is directly involved in thymocyte loss and skewed differentiation. They also indicate that AhR activation in T cells and not in B cells suppresses the immunization-induced increase in both T cells and B cells.

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“…Although very little is known about the endogenous function of the AhR in the immune system, TCDD has a very profound effect on immune function. In fact, T cell-dependent responses and host resistance to infection are extremely sensitive targets for modulation by AhR agonists (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Although the molecular mechanisms that underlie these effects are not entirely clear, epidemiological data suggest that exposure to pollutants that contain AhR agonists correlates with diminished host resistance, altered immune function, and an increased incidence of influenza and other respiratory infections (27)(28)(29), suggesting a possible cause and effect relationship between exposure to AhR ligands and altered host resistance to infection.…”

mentioning

confidence: 99%

Aryl Hydrocarbon Receptor Activation Impairs the Priming but Not the Recall of Influenza Virus-Specific CD8+ T Cells in the Lung

Lawrence

Roberts

Neumiller

et al. 2006

The Journal of Immunology

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The response of CD8+ T cells to influenza virus is very sensitive to modulation by aryl hydrocarbon receptor (AhR) agonists; however, the mechanism underlying AhR-mediated alterations in CD8+ T cell function remains unclear. Moreover, very little is known regarding how AhR activation affects anamnestic CD8+ T cell responses. In this study, we analyzed how AhR activation by the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the in vivo distribution and frequency of CD8+ T cells specific for three different influenza A virus epitopes during and after the resolution of a primary infection. We then determined the effects of TCDD on the expansion of virus-specific memory CD8+ T cells during recall challenge. Adoptive transfer of AhR-null CD8+ T cells into congenic AhR+/+ recipients, and the generation of CD45.2AhR−/−→CD45.1AhR+/+ chimeric mice demonstrate that AhR-regulated events within hemopoietic cells, but not directly within CD8+ T cells, underlie suppressed expansion of virus-specific CD8+ T cells during primary infection. Using a dual-adoptive transfer approach, we directly compared the responsiveness of virus-specific memory CD8+ T cells created in the presence or absence of TCDD, which revealed that despite profound suppression of the primary response to influenza virus, the recall response of virus-specific CD8+ T cells that form in the presence of TCDD is only mildly impaired. Thus, the delayed kinetics of the recall response in TCDD-treated mice reflects the fact that there are fewer memory cells at the time of reinfection rather than an inherent defect in the responsive capacity of virus-specific memory CD8+ cells.

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

Cited by 59 publications

References 34 publications

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Constitutively Active Aryl Hydrocarbon Receptor Expressed Specifically in T-Lineage Cells Causes Thymus Involution and Suppresses the Immunization-Induced Increase in Splenocytes

Aryl Hydrocarbon Receptor Activation Impairs the Priming but Not the Recall of Influenza Virus-Specific CD8+ T Cells in the Lung

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