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

PLoS One. 2015 Oct 21;10(10):e0140808. doi: 10.1371/journal.pone.0140808. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Asthma / chemically induced
  • Asthma / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8 Antigens / genetics
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Female
  • Interferon gamma Receptor
  • Interferon-gamma / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Lung / immunology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin
  • Pneumonia / immunology*
  • Receptors, Interferon / biosynthesis
  • Sex Factors

Substances

  • CD8 Antigens
  • CD8alpha antigen
  • Receptors, Interferon
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin

Grants and funding

This work was supported in part by a Grant-in-Aid for Scientific Research (No. 25461164) to I.O. (https://www.jsps.go.jp/english/index.html), a Grant-in-Aid for Research Activity Start-up (No. 25893222) to T.M. (https://www.jsps.go.jp/english/index.html), the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan to T. Kawano (http://www.shigaku.go.jp/s_home.htm), and by the Matching Fund Subsidy for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan to I.O., T.M., and T. Kawano (http://www.mext.go.jp/english/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.