Immunotoxicity target cells

Cells of the T cell lineage appear to be more sensitive to the immunomodulatory effects of Pb compared to other lymphoid populations. In addition, there are considerable differences in sensitivity across various T cell subpopulations [38 41], This differential sensitivity has become another major hallmark of Pb-induced immunotoxicity, although most data implicate T cells as indirect targets of Pb immunotoxicity. Both in vivo and in vitro observations of T-dependent immune responses in the presence of Pb suggest that T helper function and Th-dependent cytokines are skewed preferentially toward Th2 reactivities. Smith and Lawrence [42] found that Pb inhibited antigen presentation and stimulated a T cell clone of the Thl phenotype. McCabe and Lawrence [38] were the first to show that Pb inhibited Thl stimulation while it promoted presentation to Th2 clones. Heo and colleagues [39 41] provided both in vitro and in vivo results supporting this immunomodulation by Pb. 

Perhaps the environmental chemical most studied with regard to effects on the immune system has been 2,3,7,8-tetrachlorodibenzo-p-dioxin, which is also known as TCDD or dioxin . While it appears that dioxin may affect multiple cell types, it is apparent that the B cell is an especially sensitive target. The mechanism of action for the immunotoxic effects of dioxin remains poorly understood. It is well established that many of the actions of dioxin, including inhibition of the primary antibody response, are mediated by a specific cytosolic receptor, termed the aryl hydrocarbon receptor (AhR). AhR exhibits a profile of activity similar to steroid receptors in that the ligand-activated receptor undergoes a nuclear... 

A very interesting opportunity is the fact that the very same test can be performed ex vivo after immunomodulatory treatment or intoxications [68-70]. The example of the whole blood immunotoxicity assay shows that with the relatively easy access to human primary cells, the field is predestined for using cells from the target species of interest. Noteworthy, protocols for other immune function assays using whole blood incubations available affording similar advantages [71, 72],... 

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