Time Course of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-Induced Thymic Atrophy in the Wistar Rat

Heer, Cees de; Verlaan, A. P. J.; Penninks, André; Vos, J.G.; Schuurman, Henk‐Jan; Loveren, Henk Van

doi:10.1006/taap.1994.1185

Cited by 42 publications

(14 citation statements)

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“…Likewise, TCDD induces thymic atrophy and triggers subtle or no alterations in the T-cell subpopulations of adult mice (Kerkvliet and Brauner 1990;Rhile et al 1996), which is consistent with the findings of the current study. However, it is worth mentioning that strong depletion of DP T cells has been found in adults rats acutely exposed to TCDD (De Heer et al 1994). Interestingly, a combination of pregnancy and TCDD caused a dramatic change in T-cell subsets with an increase in the percentages of sP CD4 + , sP CD8 + and DN T cells and a decrease in the percentage of DP T cells.…”

Section: Discussionmentioning

confidence: 97%

Effect of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on maternal immune response during pregnancy

Camacho

Nagarkatti

2004

Archives of Toxicology

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Whether pregnancy-induced immunosuppression when combined with exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) could exacerbate immunotoxicity has not been previously investigated. The current study evaluated the immune status of C57BL/6 pregnant and virgin mice following exposure to TCDD. To this end, syngeneically pregnant or virgin female mice were injected intraperitoneally with 10 micro g/kg TCDD. Pregnancy alone significantly decreased thymic cellularity and J11d expression as well as induced changes in T-cell subsets. TCDD treatment caused significant thymic atrophy in pregnant mice as early as 48 h after exposure, but this effect was apparent in virgin mice only after 72 h. TCDD treatment also caused more marked alterations in thymic T-cell subpopulations of pregnant mice when compared to the virgin mice, with a decrease in the percentage of double-positive T cells and an increase in the percentage of single-positive (sP CD4(+) or sP CD8(+)) and double-negative T cells. Moreover, the proliferative responses of thymocytes, but not splenocytes, to mitogens were significantly altered in TCDD-treated pregnant mice when compared to the TCDD-treated virgin mice. Furthermore, no significant changes in the expression of CD4, CD8, B220 and NK1.1 markers were found in splenocytes from TCDD-treated virgin and pregnant mice. Immunization of mice with a superantigen caused a similar immunotoxic response in TCDD-treated pregnant and virgin mice with a decreased lymph node cellularity and lower percentages and cell numbers of Vbeta3(+) and Vbeta11(+) T cells. Together, the results of the current study demonstrate for the first time that pregnancy augments the sensitivity to TCDD-induced immunotoxicity in the thymus, but not in secondary lymphoid organs.

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Section: Discussionmentioning

confidence: 97%

Effect of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on maternal immune response during pregnancy

Camacho

Nagarkatti

2004

Archives of Toxicology

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“…The thymus is a sensitive target for 2,3,7,8-TCDD in rats (De Heer et al 1994) and other laboratory animals, with thymus atrophy being attributed to reduced maturation of the thymocytes (Blaylock et al 1992;Greenlee et al 1985) and reduced seeding of the thymus by bone marrow progenitors (Fine et al 1990). In addition to noticeable eects on the actual thymus, populations of mature circulating T-lymphocytes were also impaired.…”

Section: Discussionmentioning

confidence: 99%

“…5 lg/kg body wt. at weaning, a dosage which has been demonstrated to be immunotoxic in laboratory rats (De Heer et al 1994;Ross et al 1996c). Therefore this group served as a positive control in the study.…”

Section: Discussionmentioning

confidence: 99%

Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or 2,3,7,8-TCDD

Ross¹,

Swart²,

Vliet

et al. 1997

Archives of Toxicology

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While the immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well established, the eects of complex environmental mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) are poorly understood. Many PHAHs, including the polychlorinated-biphenyls (PCBs), -dibenzofurans (PCDFs), and dibenzo-p-dioxins (PCDDs), possess`dioxin-like' activities, and accumulate in the aquatic food chain. Organisms occupying high trophic levels may therefore be exposed to concentrations which may present an immunotoxic risk. In this study, pregnant PVG rats were administered a daily oral dose of 1 ml of the following during pregnancy and lactation: (1) oil extracted from herring caught in the relatively uncontaminated Atlantic Ocean; (2) oil extracted from herring caught in the contaminated Baltic Sea; or (3) the Atlantic herring oil extract spiked with 2,3,7,8-TCDD. The daily intakes of aryl hydrocarbon (Ah)-receptor dependent toxic equivalents (TEQ) for mothers were 0.3 in the Atlantic group, 2.1 in the Baltic group, and 134 ng/kg body wt. in the 2,3,7,8-TCDD positive control group. Immune function and host resistance to rat cytomegalovirus (RCMV) were assessed in ospring aged 11, 25, 46 or 59 days. Rat pups in the positive control TCDD-spiked group exhibited immunosuppression characterized by reduced thymus weight and cellularity, reduced thymocyte and splenocyte proliferative responses to T-dependent mitogens in vitro, reduced virus-associated natural killer (NK) cell and speci®c antibody responses. While less pronounced, a similar pattern of eects was observed in the rat pups exposed only to the Baltic Sea herring oil. These immunotoxic eects were transient in both exposure groups, with a time-related recovery in immune function possibly due to the half-life of TCDD in rats and the waning exposure levels in the rapidly growing pups. We previously demonstrated that the same Baltic Sea herring led to impaired natural killer cell and Tlymphocyte function in harbour seals during the course of a long-term captive feeding study. The collective results of these studies in rats and seals indicate the immunotoxic potential of environmental mixtures at current levels in the aquatic environment, and suggest that the developing immune system of young mammals may be at particular risk.

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“…Thymus atrophy induced by exposure of mice to TCDD is characterized by decreases in tissue weight and cell number that are mainly attributable to a decrease in CD4 + CD8 + double-positive (DP) cells [10][11][12][13], the predominant population of thymocytes. Skewing of thymocyte differentiation toward CD8 single-positive (SP) T cells [10,12,14,15] and a consequent decrease in the ratio of CD4 SP cells/CD8 SP cells are other distinctive features of the responses to TCDD exposure.…”

Section: Introductionmentioning

confidence: 99%

Constitutive activation of the aryl hydrocarbon receptor in T-lineage cells induces thymus involution independently of the Fas/Fas ligand signaling pathway

Nagai

Kubo

Ryo

et al. 2006

International Immunopharmacology

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Time Course of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-Induced Thymic Atrophy in the Wistar Rat

Cited by 42 publications

References 0 publications

Effect of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on maternal immune response during pregnancy

Effect of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) on maternal immune response during pregnancy

Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or 2,3,7,8-TCDD

Constitutive activation of the aryl hydrocarbon receptor in T-lineage cells induces thymus involution independently of the Fas/Fas ligand signaling pathway

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