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(ii) The proposed model of pharmacological-interaction (PI concept) where the drug or metabolite+endogenous peptide occupies the space between the HLA of the APC and the TCR of a T nave lymphocyte with a non-covalent, temporary bond and interactions occur regardless of drug processing by the APC, directly inducing T-cell activation, or (iii) Through the altered self-peptide repertoire model, in which a drug linked to an altered endogenous peptide binds, in turn, instead, to an HLA or TCR, changing the binding conformation and is recognized as immunogenic, without the processing of the medication.22 Through cell-to-cell interactions, APCs are believed to activate drug-specific T cells, with the help of co-stimulatory molecules such as OX40, which prevent T cells from being inhibited by regulatory T cells (Tregs).23 Activated Th2 cells release cytokines, including IL-4, IL-13, and IL-5, inducing eosinophilia in tissues and peripheral blood.23 Furthermore, eotaxin produced by keratinocytes and TARC (thymus and activation-regulated chemokine) produced by dendritic cells (DC), promote the harmful accumulation of eosinophils in the skin and other internal organs

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