Increased type 2 cytokine expression by both CD4⁺ CD45RO⁺ T cells and CD8⁺ CD45RO⁺ T cells in blood circulation is associated with high serum IgE but not with atopic dermatitis

Type 2 cytokines, such as interleukin-4 (IL-4) and IL-13, are associated with immunoglobulin E (IgE) production. This association has also been observed in CD8⁺ T cells from patients infected with leprosy and human immunodeficiency virus (HIV). Using intracellular cytokine staining and flow cytometry, the cytokine profile [IL-2, IL-4, IL-10, IL-13, and interferon (IFN)-γ] of both CD4⁺ and CD8⁺ memory/effector T cells circulating in atopic dermatitis (AD) patients was investigated at the single cell level. The levels of type 2 cytokines in CD4⁺ T cells or CD8⁺ T cells in AD patients with high levels of serum IgE (AD-H), low levels of serum IgE (AD-L), and healthy controls were compared. Increased production of IL-4 and IL-13 in both CD4⁺ CD45RO⁺ T cells and CD8⁺ CD45RO⁺ T cells after 4 h in vitro stimulation with phorbol 12-myristate 13-acetate and ionomycin, was more prominent in AD-H patients than in AD-L patients or healthy controls, whereas IFN-γ-producing CD4⁺ CD45RO⁺ T cells and CD8⁺ CD45RO⁺ T cells were relatively diminished in AD-H patients. CD4⁺ T cells and CD8⁺ T cells from AD-H patients, cultured for 48 h with phorbol 12-myristate 13-acetate and ionomycin, released larger amounts of IL-4 and IL-13 but smaller amounts of IFN-γ than both types of cells from AD-L patients or healthy controls. In addition, when stimulated with immobilized anti-CD3 monoclonal antibody (MoAb) and anti-CD28 MoAb, CD4⁺ CD45RO⁺ T cells and CD8⁺ CD45RO⁺ T cells from AD-H patients contained more IL-4-producing cells but fewer IFN-γ-producing cells compared with healthy controls. Finally, spontaneous mRNA expression of IL-4 in blood CD8⁺ CD45RO⁺ T cells isolated from AD-H patients was increased, as determined by reverse transcriptase-polymerase chain reaction. Therefore, in AD patients with high IgE levels, type 2 cytokine (IL-4 and IL-13) expression is associated with IgE production, in both CD4⁺ CD45RO⁺ T cell and CD8⁺ CD45RO⁺ T cell subsets.