Immune cell functions in industrial workers after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: dissociation of antigen-specific T-cell responses in cultures of diluted whole blood and of isolated peripheral blood mononuclear cells.
A comparative analysis was performed of the phenotype and function of peripheral blood leukocytes of two age-matched cohorts of industrial workers in chemical plants, one of which was exposed occupationally to high concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Median actual TCDD burdens were 116 ng/kg and 4 ng/kg, respectively. The phenotype analysis of peripheral blood mononuclear cells (PBMC) revealed no significant differences in the proportions of CD3, CD4, or CD8+ T lymphocytes, of CD16+ natural killer cells, and of CD19+ B lymphocytes. However, in PBMC of the TCDD-exposed workers; the proportion of CD8+ memory T cells (CD45R0+) was significantly higher, and that of lymphocytes with naive phenotype (CD45RA+) was significantly lower than in PBMC of the control group. Polyclonal and antigen-specific T-cell activation was assessed in parallel in isolated PBMC as well as in diluted whole blood cultures. In both culture systems the polyclonally stimulated cytokine release did not differ significantly between the two cohorts; however, we found a significantly reduced interferon gamma release in diluted whole blood cultures but not in isolated PBMC cultures of the TCDD-exposed cohort when we performed an antigen-specific T-cell stimulation with tetanus-toxoid. Therefore, we propose that exposure of individuals to high doses of TCDD can partially impair in the "blood milieu" those T-cell/monocyte interactions that are essential for antigen-specific T-cell responses, whereas isolated PBMC of the same donors appear functionally less affected.
Ernst
M
M
Forschungszentrum Borstel, Abteilung Immunologie und Zellbiologie, Germany. mernst@fz-borstel.de
Flesch-Janys
D
D
Morgenstern
I
I
Manz
A
A
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D002478:Cells, Cultured; D015331:Cohort Studies; D006801:Humans; D066298:In Vitro Techniques; D007221:Industry; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010641:Phenotype; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D000072317:Polychlorinated Dibenzodioxins; D007371:Interferon-gamma