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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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CD1d1 (CD1−/−)  mutant mice and wild-type controls (CD1+/+) were immunized  on day 0 and challenged daily  with aerosolized OVA on days  14–20. The number of eosinophils in lung tissue was similar in  both groups of mice. Solid bars,  mean (n = 9–11 per group).
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Figure 6: CD1d1 (CD1−/−) mutant mice and wild-type controls (CD1+/+) were immunized on day 0 and challenged daily with aerosolized OVA on days 14–20. The number of eosinophils in lung tissue was similar in both groups of mice. Solid bars, mean (n = 9–11 per group).

Mentions: To elucidate if the suppression of the allergic immune response seen after NK1.1+ cell depletion requires NK cells or NKT cells, CD1d1 mutant mice, which selectively lack NKT cells (group 17), were immunized and OVA challenged. Immunization and OVA exposure (seven times) of mice deficient in NKT cells led to the development of a pulmonary eosinophil-rich inflammation similar to that observed in corresponding wild-type animals (Fig. 6). CD1d1 mutant and wild-type mice also exhibited similar levels of OVA-specific IgE (4,342.9 ± 1,054.3 and 6,814.8 ± 2,702.9 U/ml, respectively). The numbers of IL-4– and IFN-γ–producing spleen cells in immunized and allergen-challenged CD1d1 mutant and wild-type mice were determined by the ELISPOT method. There was a tendency, although statistically insignificant, of reduced numbers of IL-4–producing unstimulated and OVA-stimulated spleen cells from CD1d1 mutant mice compared with wild-type mice (5.4 ± 1.2 vs. 16.2 ± 6.0 SFCs/106 CD3+ unstimulated cells and 150.0 ± 27.1 vs. 418.2 ± 212.8 SFCs/106 CD3+ OVA-stimulated cells). The number of unstimulated IFN-γ–producing cells was increased in CD1d1 mutant mice compared with wild-type mice (60.0 ± 17.2 vs. 15.4 ± 7.8 SFCs/106 CD3+ cells; P < 0.05). There was also a tendency of increased numbers of OVA-stimulated IFN-γ–producing cells from mutant mice compared with wild-type animals (134.4 ± 54.1 vs. 40.9 ± 11.9 SFCs/106 CD3+ cells).


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)

CD1d1 (CD1−/−)  mutant mice and wild-type controls (CD1+/+) were immunized  on day 0 and challenged daily  with aerosolized OVA on days  14–20. The number of eosinophils in lung tissue was similar in  both groups of mice. Solid bars,  mean (n = 9–11 per group).
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Related In: Results  -  Collection

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Figure 6: CD1d1 (CD1−/−) mutant mice and wild-type controls (CD1+/+) were immunized on day 0 and challenged daily with aerosolized OVA on days 14–20. The number of eosinophils in lung tissue was similar in both groups of mice. Solid bars, mean (n = 9–11 per group).
Mentions: To elucidate if the suppression of the allergic immune response seen after NK1.1+ cell depletion requires NK cells or NKT cells, CD1d1 mutant mice, which selectively lack NKT cells (group 17), were immunized and OVA challenged. Immunization and OVA exposure (seven times) of mice deficient in NKT cells led to the development of a pulmonary eosinophil-rich inflammation similar to that observed in corresponding wild-type animals (Fig. 6). CD1d1 mutant and wild-type mice also exhibited similar levels of OVA-specific IgE (4,342.9 ± 1,054.3 and 6,814.8 ± 2,702.9 U/ml, respectively). The numbers of IL-4– and IFN-γ–producing spleen cells in immunized and allergen-challenged CD1d1 mutant and wild-type mice were determined by the ELISPOT method. There was a tendency, although statistically insignificant, of reduced numbers of IL-4–producing unstimulated and OVA-stimulated spleen cells from CD1d1 mutant mice compared with wild-type mice (5.4 ± 1.2 vs. 16.2 ± 6.0 SFCs/106 CD3+ unstimulated cells and 150.0 ± 27.1 vs. 418.2 ± 212.8 SFCs/106 CD3+ OVA-stimulated cells). The number of unstimulated IFN-γ–producing cells was increased in CD1d1 mutant mice compared with wild-type mice (60.0 ± 17.2 vs. 15.4 ± 7.8 SFCs/106 CD3+ cells; P < 0.05). There was also a tendency of increased numbers of OVA-stimulated IFN-γ–producing cells from mutant mice compared with wild-type animals (134.4 ± 54.1 vs. 40.9 ± 11.9 SFCs/106 CD3+ cells).

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