Abstract
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 cd8α-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-γ 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-γ 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-γ by CD8+ T cells and the lower expression of IFN-γ receptor on CD4+ T cells in females compared with males.
Highlights
Bronchial asthma is characterized by chronic airway inflammation in response to inhaled allergens, leading to wheezing, coughing, chest tightness and shortness of breath
The number of CD4+ T cells in bronchoalveolar lavage (BAL) fluids of WT mice was significantly higher in female mice than in male mice, whereas CD8+ T cell counts in BAL fluids were not different between male and female mice (Fig 1C)
The sex differences in differential cell counts and the number of CD4+ T cells in BAL fluids were abrogated in CD8KO mice (Fig 1B and 1D)
Summary
Bronchial asthma is characterized by chronic airway inflammation in response to inhaled allergens, leading to wheezing, coughing, chest tightness and shortness of breath. Despite advances in both short- and long-term control medications for asthma, the incidence rate of asthma deaths is 1.4 per 10,000 persons with asthma in general population, but can be as high as 5.8 per 10,000 persons with asthma, especially in people aged 65 or over in the USA [1]. The rate of relapse after discharge from the emergency department for acute asthma among adults is higher in women than in men [6], which is likely associated with sex differences in resistance to controller medications such as inhaled corticosteroids [7]
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