Direct suppression of superantigen-induced IgM secretion in human lymphocytes by 2,3,7,8-TCDD.
The superantigen, toxic shock syndrome toxin (TSST-1), can activate T-cells to proliferate and secrete lymphokines and can act as a nominal antigen to induce proliferation and immunoglobulin secretion in human B-cells. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant that produces potent suppression of murine immunocompetence. The present studies were initiated in order to examine the direct effects of TCDD upon human lymphocytes stimulated with TSST-1. TCDD had no effect upon TSST-1-induced T-cell proliferation and produced only a nonsignificant suppression (15%) of TSST-1-induced B-cell proliferation only at the highest concentration tested (30 nM). In contrast, TSST-1-induced B-cell differentiation, as manifested by IgM secretion, was significantly suppressed by TCDD over the concentration range tested (i.e., 0.3 to 30 nM) in trials using B-cells from four separate donors. However, there was obvious variability in the sensitivity to TCDD in that we detected IC50 values of < 0.3, < 0.3, approximately 5.0, and approximately 25.0 nM in the four trials. These results suggest that human B-cell function, following stimulation by TSST-1, can be modulated by direct exposure to TCDD.
Wood
S C
SC
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Holsapple
M P
MP
D001402:B-Lymphocytes / Q000187:drug effects; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects
D001427:Bacterial Toxins; D004768:Enterotoxins; D007075:Immunoglobulin M; D000072317:Polychlorinated Dibenzodioxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal