Cross-Reactivity in Murine Fluoroquinolone Photoallergy: Exclusive Usage of TCR Vβ13 by Immune T Cells That Recognize Fluoroquinolone-Photomodified Cells

Abstract

AbstractFluoroquinolone antibacterial agents are well known to elicit photosensitivity as an adverse effect, and their cross-reactivity has been clinically documented. The photoallergenicity of fluoroquinolones is mainly derived from their photohaptenic moiety, and photomodification of skin epidermal cells with fluoroquinolones is thought to be an initial step for this photoallergy. Here we have explored, both in vivo and in vitro, T cell responses to fluoroquinolone-photomodified cells, focusing on their photoantigenic cross-reactivity. Cells were derivatized with fluoroquinolones under exposure to UV-A, and fluoroquinolone photoadducts were detected in photomodified cells by immunostaining, flow cytometry, and cell ELISA using fluoroquinolone-specific mAb. T cell-mediated hypersensitivity induced and elicited by s.c. injection of fluoroquinolone-photomodified epidermal cells was cross-reactive among six fluoroquinolones. In addition, lymph node cells from mice sensitized with fluoroquinolone-photomodified cells proliferated well in vitro not only to Langerhans cell-enriched epidermal cells photoderivatized with corresponding fluoroquinolone, but also to those photomodified with any of five other fluoroquinolones, supporting their cross-reactivity. In three fluoroquinolones tested, Th1 populations that expanded after in vitro photoantigenic stimulation of immune lymph node cells expressed the same Vβ13 of TCR. The sensitivity could be transferred by the i.v. administration of this Vβ13+ T cell line into naive recipients, in which a high percentage of Vβ13+ cells infiltrated at the challenge site. These findings suggest that these fluoroquinolones carry the same photoantigenic epitope, which is recognized by Vβ13+ T cells, leading to fluoroquinolone photosensitivity and cross-reactivity.