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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: 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.Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation.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 the  development of eosinophilic pulmonary inflammation. Animals were immunized and repeatedly challenged to aerosolized OVA (seven times). 8 h  after last exposure, lungs were processed for histologic analysis. Eosinophils are visualized by histochemical demonstration of cyanide-resistant  eosinophil peroxidase activity. Multifocal perivascular and peribronchial  eosinophilic distribution in the lung tissue is seen in immunized and IgG-treated mice 8 h after last OVA exposure (a). Corresponding mice depleted of NK1.1+ cells exhibited a few scattered eosinophilic infiltrates  only (b), or a complete absence of pulmonary inflammation (not shown).  B, bronchus; V, blood vessel. Bar, 150 μm.
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Figure 2: Effect of depleting NK1.1+ cells before immunization on the development of eosinophilic pulmonary inflammation. Animals were immunized and repeatedly challenged to aerosolized OVA (seven times). 8 h after last exposure, lungs were processed for histologic analysis. Eosinophils are visualized by histochemical demonstration of cyanide-resistant eosinophil peroxidase activity. Multifocal perivascular and peribronchial eosinophilic distribution in the lung tissue is seen in immunized and IgG-treated mice 8 h after last OVA exposure (a). Corresponding mice depleted of NK1.1+ cells exhibited a few scattered eosinophilic infiltrates only (b), or a complete absence of pulmonary inflammation (not shown). B, bronchus; V, blood vessel. Bar, 150 μm.

Mentions: Immunized and IgG-treated mice receiving seven OVA challenges exhibited at the 8 h time point a marked eosinophilia perivascularly and peribronchially in the lung (groups 7 and 9; Fig. 1, a and b, and Fig. 2 a). In contrast, corresponding mice depleted of NK1.1+ cells (groups 8 and 10) showed a clearly inhibited eosinophilia in lung tissue (Fig. 1, a and b). These mice exhibited a few scattered eosinophilic infiltrates, or a complete absence of pulmonary inflammation (Fig. 2 b). Eosinophilic infiltrates were not observed in lung tissue from SAL-exposed mice of either the IgG-treated or the NK1.1+ cell–depleted groups (groups 5 and 6; Fig. 1 a). The marked attenuation of lung tissue eosinophilia in mice depleted of NK1.1+ cells was still observed 30 h after the last OVA exposure (group 15; Fig. 1 b). At this time point, one outlier (determined by Q test) was obvious, without which the difference between IgG-treated and depleted animals had been statistically significant (P < 0.05). It is possible that this single animal (exhibiting the second most pronounced pulmonary eosinophilia in the experiment) was not successfully depleted of NK1.1+ cells after the first injection of mAb NK1.1, 2 d before immunization.


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 the  development of eosinophilic pulmonary inflammation. Animals were immunized and repeatedly challenged to aerosolized OVA (seven times). 8 h  after last exposure, lungs were processed for histologic analysis. Eosinophils are visualized by histochemical demonstration of cyanide-resistant  eosinophil peroxidase activity. Multifocal perivascular and peribronchial  eosinophilic distribution in the lung tissue is seen in immunized and IgG-treated mice 8 h after last OVA exposure (a). Corresponding mice depleted of NK1.1+ cells exhibited a few scattered eosinophilic infiltrates  only (b), or a complete absence of pulmonary inflammation (not shown).  B, bronchus; V, blood vessel. Bar, 150 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Effect of depleting NK1.1+ cells before immunization on the development of eosinophilic pulmonary inflammation. Animals were immunized and repeatedly challenged to aerosolized OVA (seven times). 8 h after last exposure, lungs were processed for histologic analysis. Eosinophils are visualized by histochemical demonstration of cyanide-resistant eosinophil peroxidase activity. Multifocal perivascular and peribronchial eosinophilic distribution in the lung tissue is seen in immunized and IgG-treated mice 8 h after last OVA exposure (a). Corresponding mice depleted of NK1.1+ cells exhibited a few scattered eosinophilic infiltrates only (b), or a complete absence of pulmonary inflammation (not shown). B, bronchus; V, blood vessel. Bar, 150 μm.
Mentions: Immunized and IgG-treated mice receiving seven OVA challenges exhibited at the 8 h time point a marked eosinophilia perivascularly and peribronchially in the lung (groups 7 and 9; Fig. 1, a and b, and Fig. 2 a). In contrast, corresponding mice depleted of NK1.1+ cells (groups 8 and 10) showed a clearly inhibited eosinophilia in lung tissue (Fig. 1, a and b). These mice exhibited a few scattered eosinophilic infiltrates, or a complete absence of pulmonary inflammation (Fig. 2 b). Eosinophilic infiltrates were not observed in lung tissue from SAL-exposed mice of either the IgG-treated or the NK1.1+ cell–depleted groups (groups 5 and 6; Fig. 1 a). The marked attenuation of lung tissue eosinophilia in mice depleted of NK1.1+ cells was still observed 30 h after the last OVA exposure (group 15; Fig. 1 b). At this time point, one outlier (determined by Q test) was obvious, without which the difference between IgG-treated and depleted animals had been statistically significant (P < 0.05). It is possible that this single animal (exhibiting the second most pronounced pulmonary eosinophilia in the experiment) was not successfully depleted of NK1.1+ cells after the first injection of mAb NK1.1, 2 d before immunization.

Bottom Line: 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.Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation.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