There is a high incidence of asthma, rhinitis, conjunctivitis and contact urticaria in workers of precious metal refineries. Symptoms are closely associated with sensitization to halogenated platinum compounds, as assessed by skin-prick test. The aim of the present study was to examine the molecular mechanisms involved by describing the T-cell receptor (TCR) repertoire distribution of peripheral blood mononuclear cells (PBMCs) without and after in vitro stimulation with sodium hexachloroplatinate.PBMCs of 17 sensitized subjects with work-related asthma and a positive skin-prick test result to sodium hexachloroplatinate and of 15 nonexposed subjects were isolated and TCR expression determined by flow cytometry. Furthermore, the sodium hexachloroplatinate-mediated in vitro effects on the frequency of Vb-expressing Tcells, the proliferation response and the expression of cell surface molecules like CD71, CD25, CD95 and HLA-DR were studied.CD3-positive lymphocytes of platinum salt-sensitized workers had a significantly higher frequency of Va2a+, Vb11+ and Vb21.3+ T-cells than controls (p<0.01, p<0.01 and p<0.001 respectively). In vitro stimulation of PBMCs from platinum saltsensitized as well as control subjects with sodium hexachloroplatinate increased the percentage of CD3-positive cells bearing specific TCRs, especially Vb5.3, Vb6.7, Vb8a, Vb20 and Vb21.3. This effect was time-and dose-dependent.The present results indicate that the frequencies of Va2a-, Vb11 and Vb21.3-bearing blood T-cells and platinum salt-induced lymphocyte proliferation are strongly enhanced in subjects who suffer from asthma due to platinum salt. In addition, in vitro stimulation with sodium hexachloroplatinate modulates the frequencies of certain Tcell receptor-bearing T-cells. Eur Respir J 2000; 16: 871±878.

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Background: Peripheral blood mononuclear cells (PBMC) of subjects allergic to the insect-derived allergen Chi t 1–9 are characterized by an allergen-induced pronounced proliferation and increased expression of activation markers (CD25, HLA-DR, CD23). T cell lines showed an elevated percentage of Vβ8a-positive cells following stimulation by Chi t 1–9. Objective: The aim of the present study was to investigate whether Vβ8a dominance plays an important role in PBMC short-term cultures (24 h) as well. The role of exogenous added cytokines, especially IL-4, has been determined. Methods: The T cell receptor repertoire was measured with 16 monoclonal antibodies to epitopes on the variable region of the β chain by flow cytometry. Patients allergic to Chi t 1–9 were compared to nonallergic subjects as well as to subjects with other occupational allergies. In addition, cytokines were determined intracellulary by flow cytometry. Studies were performed with PBMC cultured for 24 h. Results: After cultivation for 24 h without or with different stimuli (cytokines, allergen, phytohaemagglutinin), changes in the T cell receptor profile and the cytokine profile were measurable compared to the baseline value (without cultivation). Stimulation with IL-4 revealed increased percentages of Vβ8a-expressing cells in Chi t 1–9-sensitized patients. This IL-4-induced Vβ8a increase did not occur in PBMC from the two control subject groups (non-allergic and allergic to other allergens than Chi t 1–9). Conclusion: In conclusion, the dominance of certain T cell receptor types seems to arise due to the exposure to specific allergens and cytokine production. Some T cell receptors are often affected, for example Vβ8a, whereas others only show minor variations. Vβ8a expression obviously plays an important role in Chi t 1–9 allergy.