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

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.

Effects of Nigella sativa oil on Th1/Th2, cytokine balance, and improvement of asthma control in children

“…Several clinical studies reported a significant increase in the percentage of CD4+ and CD8+ T cells producing IL-4 in asthmatic children. 22,23 This finding suggests that IL-4 is not only produced by CD4+ Th2 cells, but also by CD8+ T cells. While it is well established that CD4+ T lymphocytes play a crucial role in the initiation, progression, and persistence of asthma, the role of CD8+ T cells is less understood.…”

The Cell Research Trends of Asthma: A Stem Frequency Analysis of the Literature

“…Many studies have reported that the expression of its granular proteins has functions relevant to the features of asthma, including histopathologic changes, reversible airway narrowing, and bronchial hyperreactivity [ 41 – 44 ]. The activated T cells in the airway wall are associated with inflammation of asthma [ 45 , 46 ], and the subsets of T cell antigens have attracted extensive attention by researchers, such as the T cells of CD4+(T helper) [ 47 – 51 ], CD8+ [ 52 – 54 ], CD25+ [ 55 ], CD28 [ 56 , 57 ], CD29 [ 58 , 59 ], CD39+, and CD73 [ 60 – 63 ]. The imbalance of different subsets and the regulatory mechanism are the research emphasis of this field [ 64 – 67 ].…”

Novel Toll-Like Receptor 9 Agonist Derived from <b><i>Cryptococcus neoformans</i></b> Attenuates Allergic Inflammation Leading to Asthma Onset in Mice

“…Bronchoalveolar lavage (BAL) fluids were prepared as previously described [25]. Briefly, BAL samples collected on day 5 after OVA inhalation (with 2 × 0.25 mL chilled PBS through a cannula inserted in the trachea) were centrifuged at 450 g for 10 min at 4°C.…”

“…For cytokine assay, the entire lungs were excised 1 day after OVA inhalation and homogenized in chilled 0.1% Triton-X PBS with 1% protease inhibitor (Sigma-Aldrich). After centrifugation at 15,000 g for 15 min at 4°C, the supernatants were stored at −80°C [25].…”