Involvement of immune tolerance systems in the onset of HLA allele-specific drug-induced immunotoxicity

Abstract

[Aim] We generated a transgenic mouse carrying HLA-B*57:01 to reproduce abacavir-induced idiosyncratic toxicity. Here, to observe clear toxic phenotype, we eliminated immunosuppressive factors (PD-1 and CD4⁺ T cells) in the mouse.

[Results] Depleting CD4⁺ T cells increased memory CD8⁺ T cells by exposure to abacavir, and exacerbated PD-1 expression. In addition, depletion of CD4⁺ T cells in HLA-B*57:01-Tg/PD-1^-/- dramatically increased memory CD8⁺ T cells and induced skin redness. These results infer blockade of immunosuppression should be important in reproducing HLA-mediated immunotoxicity.