HgCl(2)-induced human lymphocyte activation in vitro: a superantigenic mechanism?
Mercuric chloride (HgCl(2)) has been proposed to be a mitogen for human blood lymphocytes in vitro. In our previous study, we demonstrated that HgCl(2) preferentially stimulates the CD4+ T cell subset to blast transformation and DNA synthesis and that the reaction is dependent on CD14+ accessory cells. In order to characterise the responding cells further and to elucidate the mechanism of T cell activation, the T cell receptor (TCR) Vbeta chain expression of the blast-transformed cells was analysed by monoclonal antibodies and flow cytometry. The 22 TCR-Vbeta-specific antibodies used were found to react with 55-80% of the naive CD4+ and CD8+ blood T cells from the different donors. Six to 18% of the lymphocytes, mainly CD4+ T cells, were blast transformed after addition of HgCl(2). The distribution of the lymphoblasts carrying certain TCR Vbeta chains were skewed, and 15-40% expressed the TCR Vbeta2 chain. Furthermore, if cells were pretreated for 5 days with HgCl(2), whereafter recombinant interleukin-2 in fresh medium was added, the TCR Vbeta7+ T cell subset was also stimulated to blast transformation. The superantigen staphyloccal enterotoxin B, as a control, induced blast transformation in 10-26% of the lymphocytes, mainly CD4+ T cells, which were, as expected, positive for Vbeta3, Vbeta12, Vbeta14 or Vbeta17. We conclude that HgCl(2) has characteristics of a superantigen, activating the human lymphocytes in a Vbeta-chain-selective manner in vitro.
Loftenius
A
A
Division of Dental Toxicology, Department of Basic Oral Sciences, Karolinska Institute, Huddinge, Sweden.
Ekstrand
J
J
Möller
E
E
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003723:Dental Amalgam / Q000009:adverse effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000009:adverse effects*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D018089:Superantigens; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D008627:Mercuric Chloride; D003723:Dental Amalgam