Cytotoxic mechanisms in different forms of T-cell-mediated drug allergies
| Autor: | Petra C. Kuechler, Werner J. Pichler, S. Schmid, Markus Britschgi, B. Grabscheid, Y. Hari |
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| Rok vydání: | 2004 |
| Předmět: |
Cytotoxicity
Immunologic Pore Forming Cytotoxic Proteins T cell T-Lymphocytes Immunology chemical and pharmacologic phenomena Biology Granzymes Natural killer cell Cell Line Interleukin 21 medicine Immunology and Allergy Cytotoxic T cell Humans fas Receptor Antigen-presenting cell Membrane Glycoproteins Perforin Serine Endopeptidases hemic and immune systems Natural killer T cell Molecular biology medicine.anatomical_structure biology.protein Drug Eruptions CD8 |
| Zdroj: | Allergy. 59(6) |
| ISSN: | 0105-4538 |
| Popis: | Background: Cytotoxic mechanisms are involved in different forms of drug induced exanthems. Methods: Here we compare the killing pathways of CD4+, CD8+ and CD4/CD8+ T-cell lines (TCL) and clones derived from patients suffering from maculopapular, bullous and pustular drug eruptions. In vitro, perforin and Fas-mediated killing was analysed in cytotoxicity assays against autologous Epstein–Barr virus (EBV)-transformed B-cell lines, Fas-transfected mouse lymphoblasts and natural killer (NK)-target cells. In addition, affected skin lesions and the TCL and clones were stained for perforin and FasL-expression. Results: We detected perforin and some FasL-mediated killing in all three types of exanthems. Some of the drug-specific T-cell clones analysed exerted mainly perforin-, other more FasL-mediated killing showing no strict relationship between their perforin- and Fas-mediated cytotoxic capacity. Using a cell culture method focusing on the generation of cytotoxic T cells, we detected drug-specific CD8+, TCRαβ+ T cells, which failed to proliferate to drug presentation by antigen presenting cells but killed in a drug dependent way. Interestingly, these cells had substantial natural killer-like T cell(s) like features as they were CD56+ and CD94+ and had the ability to kill the NK-sensitive cell line K562. Conclusion: Our data underline the important role of cytotoxic mechanisms in different forms of drug induced exanthems and suggest that even some T cells with NK-like characteristics may be involved in drug hypersensitivity. |
| Databáze: | OpenAIRE |
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