CD8+ T cells regulated by CD4+CD25+ regulatory T cells in the early stage exacerbate the development of Dermatophagoides farinae-induced skin lesions via increasing mast cell infiltration in mice.

Atopic dermatitis is a chronic inflammatory skin disease associated with CD4+ Th2 cell-shifted immune responses. Although the infiltration of skin lesions by CD8+ T cells has been recognized, their roles have not been fully defined. In this study, we examined the relationship between CD4+ and CD8+ cells in antigen-induced skin lesions of mice. BALB/c mice were repeatedly challenged with Dermatophagoides farinae (Der f) applied to the right ear nine times. Pre-treatment with anti-CD4 monoclonal antibody (mAb) during the third to sixth challenges, but not the post-treatment during the sixth to ninth challenges, exacerbated the development of Der f-induced ear swelling; pre-treatment with anti-CD25 mAb, which depletes regulatory T cells (Tregs), also exacerbated the lesions. Furthermore, the number of CD8+ T cells in lymph nodes was augmented by these pre-treatments. These findings prompted us to examine the effect of anti-CD8 mAb. Pre-treatment with anti-CD8 mAb, but not post-treatment, strongly inhibited the development of Der f-induced ear swelling; additionally, the epidermal hyperplasia and infiltration of mast cells were inhibited by the pre-treatment. Collectively, we revealed that CD8+ T cells regulated by CD4+CD25+ Tregs in the early stage are key contributors to the development of Der f-induced skin lesions via increasing mast cell infiltration, indicating that CD8+ T and Tregs could be potential therapeutic targets for atopic dermatitis.