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Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice.

Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, Chambers BJ, Hong S, Van Kaer L, Ljunggren HG, Korsgren O - J. Exp. Med. (1999)

Bottom Line: Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation.Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization.These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Neuroscience, Lund University Hospital, 221 85 Lund, Sweden. Magnus.Korsgren@mphy.lu.se

ABSTRACT
The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

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(a and b) Cytokine production by splenic cells after allergen  challenge in IgG-treated and NK1.1+ cell–depleted mice. Mice were immunized on day 0 and challenged daily with aerosolized OVA on days  14–20. Mean (± SEM) numbers of IFN-γ (white bars) and IL-4 (black  bars) spot-forming spleen cells (SFCs)/106 cells. The numbers of SFCs for  unstimulated cells (a) and the numbers of SFCs for cells stimulated with  OVA (b) are shown. IgG, IgG-treated animals; NK1.1, animals depleted  of NK1.1+ cells. *P < 0.05.
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Figure 5: (a and b) Cytokine production by splenic cells after allergen challenge in IgG-treated and NK1.1+ cell–depleted mice. Mice were immunized on day 0 and challenged daily with aerosolized OVA on days 14–20. Mean (± SEM) numbers of IFN-γ (white bars) and IL-4 (black bars) spot-forming spleen cells (SFCs)/106 cells. The numbers of SFCs for unstimulated cells (a) and the numbers of SFCs for cells stimulated with OVA (b) are shown. IgG, IgG-treated animals; NK1.1, animals depleted of NK1.1+ cells. *P < 0.05.

Mentions: To estimate the systemic T cell cytokine response in spleen after immunization and OVA challenge, we used ELISPOT. The number of IL-4–producing spleen cells (both unstimulated and OVA-stimulated cells) was overall lower in mice depleted of NK1.1+ cells compared with IgG-treated animals (Fig. 5, a and b). The number of OVA-stimulated IL-4–producing cells at the 8-h time point was significantly lower in NK1.1+ cell–depleted mice compared with IgG-treated animals (P < 0.05). Similar patterns were obtained for IFN-γ–producing cells (Fig. 5, a and b). Significant differences were obtained at the 8- and 30-h time points between the number of unstimulated IFN-γ–producing spleen cells from IgG-treated and NK1.1+ cell–depleted animals (P < 0.05).


Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice.

Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, Chambers BJ, Hong S, Van Kaer L, Ljunggren HG, Korsgren O - J. Exp. Med. (1999)

(a and b) Cytokine production by splenic cells after allergen  challenge in IgG-treated and NK1.1+ cell–depleted mice. Mice were immunized on day 0 and challenged daily with aerosolized OVA on days  14–20. Mean (± SEM) numbers of IFN-γ (white bars) and IL-4 (black  bars) spot-forming spleen cells (SFCs)/106 cells. The numbers of SFCs for  unstimulated cells (a) and the numbers of SFCs for cells stimulated with  OVA (b) are shown. IgG, IgG-treated animals; NK1.1, animals depleted  of NK1.1+ cells. *P < 0.05.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2192913&req=5

Figure 5: (a and b) Cytokine production by splenic cells after allergen challenge in IgG-treated and NK1.1+ cell–depleted mice. Mice were immunized on day 0 and challenged daily with aerosolized OVA on days 14–20. Mean (± SEM) numbers of IFN-γ (white bars) and IL-4 (black bars) spot-forming spleen cells (SFCs)/106 cells. The numbers of SFCs for unstimulated cells (a) and the numbers of SFCs for cells stimulated with OVA (b) are shown. IgG, IgG-treated animals; NK1.1, animals depleted of NK1.1+ cells. *P < 0.05.
Mentions: To estimate the systemic T cell cytokine response in spleen after immunization and OVA challenge, we used ELISPOT. The number of IL-4–producing spleen cells (both unstimulated and OVA-stimulated cells) was overall lower in mice depleted of NK1.1+ cells compared with IgG-treated animals (Fig. 5, a and b). The number of OVA-stimulated IL-4–producing cells at the 8-h time point was significantly lower in NK1.1+ cell–depleted mice compared with IgG-treated animals (P < 0.05). Similar patterns were obtained for IFN-γ–producing cells (Fig. 5, a and b). Significant differences were obtained at the 8- and 30-h time points between the number of unstimulated IFN-γ–producing spleen cells from IgG-treated and NK1.1+ cell–depleted animals (P < 0.05).

Bottom Line: Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation.Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization.These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Neuroscience, Lund University Hospital, 221 85 Lund, Sweden. Magnus.Korsgren@mphy.lu.se

ABSTRACT
The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.

Show MeSH
Related in: MedlinePlus