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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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Number of eosinophils in lung tissue from immunized wild-type and γ/δ T cell– deficient animals receiving seven  exposures with OVA or SAL.  Solid bars, mean (n = 6 per  group); SAL γ/δ+/+, SAL-challenged wild-type mice; OVA γ/ δ+/+, OVA-challenged wild-type mice; OVA γδ−/−, OVA-challenged γ/δ T cell–deficient  animals. An increased number of  eosinophils in lung tissue was  observed in OVA-challenged  wild-type mice compared with  corresponding SAL-exposed animals (**P < 0.01). No significant  difference was observed between  OVA-challenged wild-type mice  and γ/δ T cell–deficient mice.
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Figure 7: Number of eosinophils in lung tissue from immunized wild-type and γ/δ T cell– deficient animals receiving seven exposures with OVA or SAL. Solid bars, mean (n = 6 per group); SAL γ/δ+/+, SAL-challenged wild-type mice; OVA γ/ δ+/+, OVA-challenged wild-type mice; OVA γδ−/−, OVA-challenged γ/δ T cell–deficient animals. An increased number of eosinophils in lung tissue was observed in OVA-challenged wild-type mice compared with corresponding SAL-exposed animals (**P < 0.01). No significant difference was observed between OVA-challenged wild-type mice and γ/δ T cell–deficient mice.

Mentions: A moderate reduction, although statistically insignificant, of lung tissue eosinophilia was observed in OVA-challenged γ/δ T cell–deficient animals compared with corresponding wild-type mice (Fig. 7). Similarly, no significant difference in systemic levels of OVA-specific IgE was observed between OVA-challenged γ/δ T cell–deficient animals and corresponding wild-type mice (1,066.3 ± 314.5 and 2,567.4 ± 1,497.1 U/ml, respectively).


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)

Number of eosinophils in lung tissue from immunized wild-type and γ/δ T cell– deficient animals receiving seven  exposures with OVA or SAL.  Solid bars, mean (n = 6 per  group); SAL γ/δ+/+, SAL-challenged wild-type mice; OVA γ/ δ+/+, OVA-challenged wild-type mice; OVA γδ−/−, OVA-challenged γ/δ T cell–deficient  animals. An increased number of  eosinophils in lung tissue was  observed in OVA-challenged  wild-type mice compared with  corresponding SAL-exposed animals (**P < 0.01). No significant  difference was observed between  OVA-challenged wild-type mice  and γ/δ T cell–deficient mice.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Number of eosinophils in lung tissue from immunized wild-type and γ/δ T cell– deficient animals receiving seven exposures with OVA or SAL. Solid bars, mean (n = 6 per group); SAL γ/δ+/+, SAL-challenged wild-type mice; OVA γ/ δ+/+, OVA-challenged wild-type mice; OVA γδ−/−, OVA-challenged γ/δ T cell–deficient animals. An increased number of eosinophils in lung tissue was observed in OVA-challenged wild-type mice compared with corresponding SAL-exposed animals (**P < 0.01). No significant difference was observed between OVA-challenged wild-type mice and γ/δ T cell–deficient mice.
Mentions: A moderate reduction, although statistically insignificant, of lung tissue eosinophilia was observed in OVA-challenged γ/δ T cell–deficient animals compared with corresponding wild-type mice (Fig. 7). Similarly, no significant difference in systemic levels of OVA-specific IgE was observed between OVA-challenged γ/δ T cell–deficient animals and corresponding wild-type mice (1,066.3 ± 314.5 and 2,567.4 ± 1,497.1 U/ml, respectively).

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