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- W2023433041 abstract "Abstract Rationale A rare and potentially severe form of drug allergic reaction can lead to interstitial nephritis. Its pathophysiological mechanisms are not well understood. Methods We analyzed drug-specific T cell responses of twelve patients with presumably drug induced interstitial nephritis (most without skin symptoms) with the lymphocyte transformation test and generated drug specific T cell clones (TCC) from peripheral blood and from kidney. Cytokine and chemokine production of the drug-specific TCC was measured by ELISA. Kidney biopsies were analyzed by immunohistochemistry. Results Proliferation assays of PBMCs or TCCs isolated from the twelve patients were performed but only two patients had a proliferative response to the drug. In particular, responses to flucloxacillin of cells generated from a male treated with rifampicin, flucloxacillin and gentamycin and to penicillin of cells from another patient treated with penicillin and vancomycin. The flucloxacillin-reactive cells showed an outgrowth of T cells bearing the T-cell receptor (TCR) Vβ9 and Vβ21.3, which suggests an oligoclonal immune response to the drug-antigen. We subsequently generated flucloxacillin-specific TCCs, all expressing CD4 and αβTCRs. Analysis of cytokines (IL-4, IL-5, IL-10, IFN-γ and TNF-α) revealed a quite heterogeneous secretion pattern, and cytotoxicity was lacking. Immunohistochemical stainings demonstrated an intertubular infiltration of CD4+ and CD8+ T cells. Conclusions Drug-specific T cells may play a decisive role in drug-induced interstitial nephritis. They may be difficult to detect in peripheral blood, as they might recognize a drug metabolite only presented in the kidney. Thus, the peculiar localization in the kidney may make these T cells more harmful." @default.
- W2023433041 created "2016-06-24" @default.
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- W2023433041 date "2004-02-01" @default.
- W2023433041 modified "2023-09-27" @default.
- W2023433041 title "Involvement of drug-specific T cells in drug-induced interstitial nephritis*1" @default.
- W2023433041 doi "https://doi.org/10.1016/j.jaci.2004.01.013" @default.
- W2023433041 hasPublicationYear "2004" @default.
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