1 research outputs found
Dapsone and Nitroso Dapsone Activation of Naı̈ve T‑Cells from Healthy Donors
Dapsone
(DDS) causes hypersensitivity reactions in 0.5–3.6%
of patients. Although clinical diagnosis is indicative of a hypersensitivity
reaction, studies have not been performed to define whether dapsone
or a metabolite activates specific T-cells. Thus, the aims of this
study were to explore the immunogenicity DDS and nitroso DDS (DDS-NO)
using peripheral blood mononuclear cells from healthy donors and splenocytes
from mice and generate human T-cell clones to characterize mechanisms
of T-cell activation. DDS-NO was synthesized from DDS-hydroxylamine
and shown to bind to the thiol group of glutathione and human and
mouse albumin through sulfonamide and <i>N</i>-hydroxyl
sulphonamide adducts. Naïve T-cell priming to DDS and DDS-NO
was successful in three human donors. DDS-specific CD4+ T-cell clones
were stimulated to proliferate in response to drug via a MHC class
II restricted direct binding interaction. Cross reactivity with DDS-NO,
DDS-analogues, and sulfonamides was not observed. DDS-NO clones were
CD4+ and CD8+, MHC class II and I restricted, respectively, and activated
via a pathway dependent on covalent binding and antigen processing.
DDS and DDS-NO-specific clones secreted a mixture of Th1 and Th2 cytokines,
but not granzyme-B. Splenocytes from mice immunized with DDS-NO were
stimulated to proliferate <i>in vitro</i> with the nitroso
metabolite, but not DDS. In contrast, immunization with DDS did not
activate T-cells. These data show that DDS- and DDS-NO-specific T-cell
responses are readily detectable