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C Esser

Publications and source records attributed to C Esser.

25 records · Page 2Linked to original sources
PubMed1994

Dioxins and the immune system: mechanisms of interference. A meeting report.

2,3,7,8-Tetrachlorodibenzo-p-dioxin, or simply 'dioxin', is an environmental pollutant, infamous for its extremely high toxicity. Dioxin mimics the unknown natural ligand of the cytosolic arylhydrocarbon receptor which is conspicuously abundant in the thymus, and acts as a transcription factor upon ligand engagement. Thymus atrophy and immunosuppression have long been known to be major effects of dioxin exposure, evident at even very low doses. In a meeting held in Düsseldorf, FRG, the immunotoxicology of dioxin was discussed with respect to the pathomechanisms of dioxins on lymphocyte stem cells, thymus and T cells, cytokine modulation, and other components of the immune system. Such immunological insults may have consequences for the risk assessment of chemical compounds like dioxin.

Animals↗
PubMed1994

Proliferation inhibition and CD4/CD8 thymocyte subset skewing by in vivo exposure of C57BL/6 mice to Ah receptor-binding 3,3',4,4'-tetrachlorobiphenyl.

3,3',4,4'-Tetrachlorobiphenyl (TCB) and other Ah receptor-binding xenobiotics lead to thymus atrophy and immunosuppression, the former possibly causing the latter. In order to better understand the TCB-induced events in the murine thymus, we analyzed the effects of TCB on the proliferation capacity and maturation kinetics of different thymocyte subsets in 2-week-old C57BL/6 mice (i.e. of the Ahb-1 'dioxin-sensitive' genotype). Mice were injected with a single dose of TCB, and the development of thymocytes was followed up for 10 days using flow cytometric surface marker analysis combined with measurement of DNA content by 7-amino-actinomycin D staining. Already 2 days after exposure to TCB, fewer of the more immature thymocytes (CD4-CD8-, CD4-CD8+ alpha beta TCR-) were proliferating than in thymi from control animals. Eventually this led to a severe decrease in thymus cellularity. Moreover, a shift towards the CD4-CD8+ mature subpopulation was observed. The effects were reversible, and proliferation and CD4/CD8 subset distribution returned to normal levels within the observation period. The results are in good agreement with the data obtained previously in vitro with fetal thymus organ cultures.

Animals↗
PubMed1993

Ontogenic development of murine fetal thymocytes is accelerated by 3,3',4,4'-tetrachlorobiphenyl.

Polychlorinated hydrocarbons such as biphenyls or dioxins interfere with cellular processes by gene induction via ligand-activated binding of the cytosolic Ah-receptor to specific DNA elements. The thymus is a target organ for these processes and immunosuppression a hallmark of polychlorinated hydrocarbon toxicity. Using flow cytometry we analysed the development of thymocytes in fetal thymus organ cultures (FTOC) exposed to tetrachlorobiphenyl (TCB) for up to one week. We show that exposure to TCB changes the normal developmental pathways of fetal thymocytes within days. Overall fewer thymocytes are found in TCB-treated cultures from day 4 on, and significantly more CD8 positive thymocytes are detectable. These cells express the T-cell receptor, but not heat-stable antigen or IL2-receptor, giving them a mature phenotype. Moreover, relatively more CD4/CD8 double-negative thymocytes express CD44, a molecule involved in lymphocyte-epithelial interaction. We suggest that, at least for the CD8 single-positive thymocyte population, maturation is accelerated, and this may be due to TCB interference with physiological thymocyte-epithelial interactions.

Animals↗
PubMed1992

The murine IgG1/IgE class switch program.

Immunoglobulin class switching is controlled by cytokines. Thus, interleukin-4 (IL-4) directs class switching to both IgG1 and IgE. Consistent with this are the results reported here on restriction endonuclease analysis of active and inactive alleles of the IgH locus in IgE-producing cells. In cells that were stimulated in vitro by lipopolysaccharide and IL-4 the silent alleles preferentially switched to gamma 1, whereas in cells that were stimulated by antigen in vivo both active and inactive alleles switched to epsilon. Thirty percent of the recombined switch regions (S mu/S epsilon) contain S gamma 1 sequences, which we interpret as footprints of a previous switch to gamma 1. Since this percentage is a minimum estimate, between 30% and 100% of switching to epsilon must occur sequentially via gamma 1.

Animals↗
PubMed1989

Rapid induction of transcription of unrearranged S gamma 1 switch regions in activated murine B cells by interleukin 4.

The distribution of immunoglobulin isotypes in activated B lymphocytes can be modulated by interleukin 4 (IL4), which enhances IgG1 and suppresses IgG3. We show here that IL4 induces transcription of the region 5' adjacent to the s gamma 1 switch region within hours after onset of activation of B cells by bacterial lipopolysaccharide (LPS). Transcripts of 1.7 and 3.2 kb size containing sequences of the region 5' of s gamma 1 are detected. This transcription precedes class switch recombination between s mu and s gamma 1 and reflects the rapid opening of the s gamma 1 region as induced by IL4. This suggests that IL4 directs class switching to IgG1 by opening the s gamma 1 switch region, thus making it accessible for switch recombination.

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