Thymocyte development in Ah-receptor-deficient mice is refractory to TCDD-inducible changes

Hundeiker, Claudia; Pineau, Thierry; Cassar, Georges; Betensky, Rebecca A.; Gleichmann, Ernst; Esser, Charlotte

doi:10.1016/s0192-0561(99)00053-3

Cited by 39 publications

(40 citation statements)

References 47 publications

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“…4). Thymic atrophy (Staples et al, 1998;Hundeiker et al, 1999;Laiosa et al, 2003;Tomita et al, 2003;Nohara et al, 2005) and hepatocyte hypertrophy often measured by liver weight/total body weight (Uno et al, 2004b) are two cardinal signs of long-term AHR activation. Thymic atrophy and hepatocyte hypertrophy are just as severe in Cyp1a1/1b1 Ϫ/Ϫ as in Cyp1a1 Ϫ/Ϫ mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Oral Benzo[a]pyrene inCyp1Knockout Mouse Lines: CYP1A1 Important in Detoxication, CYP1B1 Metabolism Required for Immune Damage Independent of Total-Body Burden and Clearance Rate

Uno

Dalton²,

Dragin³

et al. 2005

Mol Pharmacol

208

216

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Section: Discussionmentioning

confidence: 99%

Oral Benzo[a]pyrene inCyp1Knockout Mouse Lines: CYP1A1 Important in Detoxication, CYP1B1 Metabolism Required for Immune Damage Independent of Total-Body Burden and Clearance Rate

Uno

Dalton²,

Dragin³

et al. 2005

Mol Pharmacol

208

216

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“…The fact that direct exposure of FTOC to TCDD reproduces the thymus involution induced by TCDD exposure in vivo (19,24) shows that TCDD directly affects the thymus, in which the target cells are present. However, the results of previous studies have suggested that two types of cells in the thymus, thymocytes (18,28) and stromal cells (24,25), are the primary targets.…”

Section: ϫ2mentioning

confidence: 99%

“…Skewing of thymocyte differentiation toward CD8 single-positive (SP) T cells is another peculiar feature of the response to TCDD exposure (18,21,22). All of these features are reproduced in vitro by direct addition of TCDD to fetal thymus organ culture (FTOC) (19,23,24), indicating that the target cells responsible for the alterations are present in the thymus. The results of previous studies that have included histological examination have led to the hypothesis that thymic stromal cells, and not thymocytes themselves, are the direct targets of TCDD that induce thymus involution (25).…”

mentioning

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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“…68 However, there are little data on the effect of dioxins during the human neonatal period. Recently, perinatal exposures to dioxins were reported to be associated with increased rather than decreased numbers of blood T cells in preschool age and school age children.…”

Section: Xenobioticsmentioning

confidence: 99%

What Caused the Epidemic ofPneumocystisPneumonia in European Premature Infants in the Mid-20th Century?

Goldman

2005

Pediatrics

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ABSTRACT. An epidemic of interstitial pneumonia principally involving premature infants occurred in Germany and nearby European countries between the 1920s and 1960s. Fatalities were due to Pneumocystis. Because the principal defenses against Pneumocystis are T cells, an acquired T-cell deficiency was postulated. A number of potential causes including malnutrition were considered. All were implausible except for a retrovirus that was benign in adults but virulent in premature infants. Furthermore, we suspect that the virus was imported into Germany from former German African colonies. Premature infants were vulnerable because of the developmental status of their T cells. Given the practices in that part of Europe at that time, the virus was most likely transmitted by contaminated blood transfusions and subsequent contamination of reusable needles and syringes used in injections. Although the epidemic ended 4 decades ago, a search for the postulated retrovirus can be conducted if tissues from affected infants are available. Pediatrics 2005;115:e725-e736. URL: www.pediatrics.org/ cgi

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Thymocyte development in Ah-receptor-deficient mice is refractory to TCDD-inducible changes

Cited by 39 publications

References 47 publications

Oral Benzo[a]pyrene inCyp1Knockout Mouse Lines: CYP1A1 Important in Detoxication, CYP1B1 Metabolism Required for Immune Damage Independent of Total-Body Burden and Clearance Rate

Oral Benzo[a]pyrene inCyp1Knockout Mouse Lines: CYP1A1 Important in Detoxication, CYP1B1 Metabolism Required for Immune Damage Independent of Total-Body Burden and Clearance Rate

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

What Caused the Epidemic ofPneumocystisPneumonia in European Premature Infants in the Mid-20th Century?

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