CD8+ T Cells Mediate Female-Dominant IL-4 Production and Airway Inflammation in Allergic Asthma

The prevalence and severity of bronchial asthma are higher in females than in males after puberty. Although antigen-specific CD8(+) T cells play an important role in the development of asthma through their suppressive effect on cytokine production, the contribution of CD8(+) T cells to sex differences in asthmatic responses remains unclear. In the present study, we investigated the sex-specific effect of CD8(+) T cells in the suppression of asthma using an ovalbumin mouse model of asthma. The number of inflammatory cells in bronchoalveolar lavage (BAL) fluid, lung type 2 T-helper cytokine levels, and interleukin-4 (IL-4) production by bronchial lymph node cells were significantly higher in female wild-type (WT) mice compared with male mice, whereas no such sex differences were observed between male and female cd8a-disrupted mice. The adaptive transfer of male, but not female, CD8(+) T cells reduced the number of inflammatory cells in the recovered BAL fluid of male recipient mice, while no such sex difference in the suppressive activity of CD8(+) T cells was observed in female recipient mice. Male CD8(+) T cells produced higher levels of IFN-gamma than female CD8(+) T cells did, and this trend was associated with reduced IL-4 production by male, but not female, CD4(+) T cells. Interestingly, IFN-gamma receptor expression on CD4(+) T cells was significantly lower in female mice than in male mice. These results suggest that female-dominant asthmatic responses are orchestrated by the reduced production of IFN-gamma by CD8(+) T cells and the lower expression of IFN-gamma receptor on CD4(+) T cells in females compared with males.