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 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.
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Chihiro
C
Ito
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Kaori
K
Okuyama-Dobashi
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Tomomitsu
T
Miyasaka
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Chiaki
C
Masuda
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Miki
M
Sato
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Tasuku
T
Kawano
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Yuichi
Y
Ohkawara
Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Toshiaki
T
Kikuchi
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Motoaki
M
Takayanagi
Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
Isao
I
Ohno
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D011014:Pneumonia / Q000276:immunology*; D017471:Receptors, Interferon / Q000096:biosynthesis; D012737:Sex Factors; D000096743:Interferon gamma Receptor
D016827:CD8 Antigens; D007371:Interferon-gamma; D015847:Interleukin-4; D010047:Ovalbumin; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C431698:CD8alpha antigen