Inorganic Lead Activates NF-κB in Primary Human CD4+T Lymphocytes

Inorganic lead (Pb) is a ubiquitous environmental contaminant that produces a variety of effects on humoral and cell mediated immune responses. The underlying molecular mechanisms for Pb's complex effects on the immune system remain obscure. Many of Pb's effects on the immune system could be explained through activation of the transcription factor, NF-κB. NF-κB is critical for T lymphocyte function and is a strong inducer of HIV-LTR activation. We demonstrate that Pb at physiologically relevant concentrations activates NF-κB in primary human CD4+T lymphocytes. Pb-induced activation of NF-κB is blocked by antibodies for p65 and p50 subunits but not cRel, indicating that the p65:p50 heterodimer (NF-κB) is involved. Functional activation of gene expression by Pb was confirmed using primary CD4+T cells transfected with an NF-κB dependent reporter gene construct. Pb did not activate NF-κB in 4 different T cell lines, suggesting that lymphoid cell lines may not be reliable surrogates for the study of transcriptional activation in human T cells. These data suggest that NF-κB may be an important molecular mediator of Pb-induced immunotoxicity.