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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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Effect of depleting NK1.1+ cells before immunization on systemic levels of OVA-specific IgE and IgG2a. Mice were immunized on  day 0 and challenged daily with aerosolized OVA on days 14–20. Plasma  was collected 8 or 30 h after last OVA challenge. Immunization and allergen exposure of IgG-treated animals induced both allergen-specific IgE  and IgG2a. In corresponding NK1.1+ cell–depleted animals, this induction  of allergen-specific IgE and IgG2a was significantly suppressed (**P < 0.01  and *P < 0.05, respectively). Solid bars, mean (n = 13–14 per group);  IgG, IgG-treated animals; NK1.1, mAb NK1.1–treated animals.
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Figure 4: Effect of depleting NK1.1+ cells before immunization on systemic levels of OVA-specific IgE and IgG2a. Mice were immunized on day 0 and challenged daily with aerosolized OVA on days 14–20. Plasma was collected 8 or 30 h after last OVA challenge. Immunization and allergen exposure of IgG-treated animals induced both allergen-specific IgE and IgG2a. In corresponding NK1.1+ cell–depleted animals, this induction of allergen-specific IgE and IgG2a was significantly suppressed (**P < 0.01 and *P < 0.05, respectively). Solid bars, mean (n = 13–14 per group); IgG, IgG-treated animals; NK1.1, mAb NK1.1–treated animals.

Mentions: To assess the peripheral immune response to immunization and allergen challenge, we measured OVA-specific IgE and IgG2a levels in plasma using ELISA. Immunization and allergen exposure of IgG-treated animals induced both OVA-specific IgE and IgG2a (Fig. 4). In corresponding NK1.1+ cell– depleted animals, this induction of OVA-specific IgE and IgG2a was significantly suppressed (P < 0.01, P < 0.05, compared with immunized and OVA-challenged mice treated with IgG).


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)

Effect of depleting NK1.1+ cells before immunization on systemic levels of OVA-specific IgE and IgG2a. Mice were immunized on  day 0 and challenged daily with aerosolized OVA on days 14–20. Plasma  was collected 8 or 30 h after last OVA challenge. Immunization and allergen exposure of IgG-treated animals induced both allergen-specific IgE  and IgG2a. In corresponding NK1.1+ cell–depleted animals, this induction  of allergen-specific IgE and IgG2a was significantly suppressed (**P < 0.01  and *P < 0.05, respectively). Solid bars, mean (n = 13–14 per group);  IgG, IgG-treated animals; NK1.1, mAb NK1.1–treated animals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192913&req=5

Figure 4: Effect of depleting NK1.1+ cells before immunization on systemic levels of OVA-specific IgE and IgG2a. Mice were immunized on day 0 and challenged daily with aerosolized OVA on days 14–20. Plasma was collected 8 or 30 h after last OVA challenge. Immunization and allergen exposure of IgG-treated animals induced both allergen-specific IgE and IgG2a. In corresponding NK1.1+ cell–depleted animals, this induction of allergen-specific IgE and IgG2a was significantly suppressed (**P < 0.01 and *P < 0.05, respectively). Solid bars, mean (n = 13–14 per group); IgG, IgG-treated animals; NK1.1, mAb NK1.1–treated animals.
Mentions: To assess the peripheral immune response to immunization and allergen challenge, we measured OVA-specific IgE and IgG2a levels in plasma using ELISA. Immunization and allergen exposure of IgG-treated animals induced both OVA-specific IgE and IgG2a (Fig. 4). In corresponding NK1.1+ cell– depleted animals, this induction of OVA-specific IgE and IgG2a was significantly suppressed (P < 0.01, P < 0.05, compared with immunized and OVA-challenged mice treated with IgG).

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