T-cell receptor repertoire expression in workers with occupational asthma due to platinum salt.
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 Vbeta-expressing T-cells, 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 Valpha2a+, Vbeta11+ and Vbeta21.3+ T-cells than controls (p<0.01, p<0.01 and p<0.001 respectively). In vitro stimulation of PBMCs from platinum salt-sensitized as well as control subjects with sodium hexachloroplatinate increased the percentage of CD3-positive cells bearing specific TCRs, especially Vbeta5.3, Vbeta6.7, Vbeta8a, Vbeta20 and Vbeta21.3. This effect was time- and dose-dependent. The present results indicate that the frequencies of Valpha2a-, V11 and Vbeta21.3-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 T-cell receptor-bearing T-cells.
Raulf-Heimsoth
M
M
Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin, Ruhr-Universität Bochum, Germany.
Merget
R
R
Rihs
H P
HP
Föhring
M
M
Liebers
V
V
Gellert
B
B
Schultze-Werninghaus
G
G
Baur
X
X
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism*; D017252:CD3 Complex / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009784:Occupational Diseases / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood*
D000954:Antigens, Surface; D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D002945:Cisplatin; C038762:disodium hexachloroplatinate