Contribution of CD4+ T Cells and Dendritic Cells to Female-Dominant Antigen-Induced T Helper Type 2 Cytokine Production by Bronchial Lymph Node Cells

Abstract

Background: After puberty, asthma severity is higher in women than in men. The underlying mechanisms of this gender difference are not fully understood. In murine models of allergic asthma, more severe airway inflammation in female mice is associated with higher levels of T helper type 2 (Th2) cytokines. The aim of this study was to investigate the contributions of CD4⁺ T cells and dendritic cells (DCs) to the differences in Th2 cytokine production between sexes. Methods: Bronchial lymph node (BLN) cells from ovalbumin (OVA)-sensitized male and female C57BL/6 mice were stimulated with OVA and anti-CD3/CD28 antibodies. The CD4⁺ T cells and DCs purified from BLN cells were cocultured with OVA in a sex-matched or mismatched fashion. The CD4⁺ T cells were also stimulated with anti-CD3/CD28 antibodies. The concentrations of interleukin (IL)-5, IL-4, IL-13 and interferon (IFN)-γ in the culture supernatants were measured. Results: The concentrations of IL-5, IL-4 and IL-13, but not IFN-γ, were significantly higher in female BLN cells stimulated with OVA than in male BLN cells. Sex differences were also observed in the CD4⁺ T cells stimulated with anti-CD3/CD28 antibodies, whereas only IL-4 was significantly different in the BLN cells stimulated with antibodies. IL-5 production by OVA-stimulated male and female CD4⁺ T cells, but not IL-4 or IL-13 production, was significantly increased in the coculture with female DCs when compared to the male DCs. Conclusions: The differences in Th2 cytokine production between sexes by the BLN cells may be attributable, at least in part, to the differing functions of CD4⁺ T cells and DCs between sexes.