Tomomitsu Miyasaka
Tohoku Medical and Pharmaceutical University, Japan
Title: Male-dominant suppressive activity of CD8+ T cells on CD4+ T cells: Assessing female-dominant allergic airway inflammation
Biography
Biography: Tomomitsu Miyasaka
Abstract
Statement of the Problem: Bronchial asthma is more severe in females than in males after puberty because of stronger Th2-oriented immune response in females. However, the mechanism of the sex difference in asthmatic immune response remains unclear. CD8+ T cells play an important role in regulating the asthma immune response through their suppressive effect on Th2 polarization within the localized lymph nodes.
Theoretical Orientation: In the present study, we investigated the sex-specific effect of CD8+ T cells on the female-predominant asthmatic immune responses using a mouse model.
Results: The number of eosinophil in bronchoalveolar lavage (BAL) fluid, lung Th2 cytokine levels, and IL-4 production by bronchial lymph node cells were significantly higher in wild-type female compared with male mice, whereas no such sex differences were observed between cd8α-disrupted (CD8KO) male and female mice. The adaptive transfer of wild-type male, but not female, CD8+ T cells reduced the number of inflammatory cells in the recovered BAL fluid of CD8KO male, but not female, recipient mice. Male CD8+ T cells produced higher levels of IFN-γ than female CD8+ T cells. Treatment with anti-IFN-γ antibody completely abrogated the sex difference in the suppressive activity of CD8+ T cells on IL-4 production from CD4+ T cells. However, IFN-γ receptor expression on CD4+ T cells was higher in male mice than in female mice. rIFN-γ treatment increased the proportion of IFN-γ receptor α+ CD4+ T cells in male naïve CD4+ T cells more than in female naïve CD4+ T cells.
Conclusion & Significance: These results suggest that female-dominant asthmatic immune responses are induced by the reduced production of IFN-γ by CD8+ T cells and the lower expression of IFN-γ receptor on CD4+ T cells caused by exposure to IFN-γ in females compared with males.