The sensitizing properties of different complex salts of platinum were defined in vivo by means of the popliteal lymph node (PLN) assay in mice. Hexa- and tetrachloroplatinates were confirmed to be highly immunogenic, inducing vigorous primary immune responses in the draining PLN following single subcutaneous injections. Flow-cytometric analysis revealed a dramatic increase in the total number of cells expressing proliferating cell nuclear antigen. The majority of these cells were of the T helper phenotype (CD4+) reflecting the T-cell dependence of the PLN response induced by Pt salts such as Na₂[PtCl₆] or Na₂[PtCl₄]. In contrast, [Pt(NH₃)₄]Cl₂ failed to elicit a significant increase in PLN cell proliferation when compared with saline-treated controls. The differential immunogenicity of the Pt compounds found in vivo directly correlated with their capacity to modulate mechanisms of receptor-mediated endocytosis in murine Langerhans cells in vitro. The reactivity of Na₂[PtCl₆] or Na₂[PtCl₄] resembled that of potent contact sensitizers in this endocytosis assay whereas [Pt(NH₃)₄]Cl₂ proved to be inert. These results suggest that [Pt(NH₃)₄]Cl₂ might be less harmful to humans than hexa- or tetrachloroplatinates. As demonstrated with Pt compounds, monitoring of direct effects of low-molecular-weight chemicals on antigen-presenting dendritic cells in vitro is able to predict their sensitizing potential in vivo.

The requirements for sensitization to complex salts of platinum were investigated in a mouse model by means of the popliteal lymph node (PLN) assay. A single subcutaneous injection of dissolved hexachloroplatinates without adjuvant induced a vigorous primary immune reaction in the draining PLN. Dose-dependent lymph node activation was determined by an increase in both PLN weight and cellularity. In C57BL/6 mice, peak reactions were obtained around day 6 after administration of 90–180 nmol Na₂[PtCl₆] or (NH₄)₂[PtCl₆] per animal. Mice primed to [PtCl₆]^2–– mounted an enhanced response upon local restimulation with suboptimal doses of the same but not unrelated compounds, indicating a specific secondary response. T cells were required to elicit PLN reactions to [PtCl₆]^2––, because athymic nude mice completely failed to respond, in contrast to their +/nu littermates. Differences between various inbred strains of mice revealed that Pt-induced PLN responses are genetically controlled. Moreover, the immunogenicity of Pt salts in mice is not confined to hexachloroplatinates, but other compounds, such as the antineoplastic agent cis-dichlorodiamine platinum, are able to induce comparable PLN reactions.

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