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Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse.

Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K - J. Exp. Med. (2004)

Bottom Line: Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18.Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro.Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, 663-8501, Japan.

ABSTRACT
Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-gamma production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

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IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. (A) AHR in response to increased concentrations of inhaled β-Mch was measured in a whole body plethysmograph. (B) Inflammatory cell composition of BALF from mice transferred with OVA-specific Th1 or Th2 cells and daily treated with intranasal administration of PBS or OVA and/or IL-18 consecutively for 3 d. Cell differential percentages were determined by light microscopic evaluation of cytospin preparation. Data are expressed as absolute numbers of cells. Representative results of five animals are shown.
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fig2: IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. (A) AHR in response to increased concentrations of inhaled β-Mch was measured in a whole body plethysmograph. (B) Inflammatory cell composition of BALF from mice transferred with OVA-specific Th1 or Th2 cells and daily treated with intranasal administration of PBS or OVA and/or IL-18 consecutively for 3 d. Cell differential percentages were determined by light microscopic evaluation of cytospin preparation. Data are expressed as absolute numbers of cells. Representative results of five animals are shown.

Mentions: We established Th1 or Th2 cells by two rounds of 7-d stimulation of CD4+ T cells obtained from OVA-specific TCR Tg BALB/c (DO11.10) mice with OVA peptide, IL-12, and anti–IL-4 or with OVA peptide, IL-4, and anti–IL-12/anti–IFN-γ in the presence of APC for 2 wk, respectively. We then transferred these newly polarized Th1 or Th2 cells i.v. into normal BALB/c mice (107 per mouse) and allowed them to adopt a resting memory phenotype in vivo (51). 30 d after passive cell transfer, these recipients were daily treated with intranasal administration of OVA and/or IL-18 for 3 d. Therefore in this experimental system, we could depict the capacity of the memory-type Th1 or Th2 cells to induce bronchial asthma in naive mice. Histopathological analysis of the airways of each group of mice revealed that Th2 cell–transferred mice showed a significant increase in the peribronchial and perivenular infiltration with eosinophils and lymphocytes when compared with normal mice after nasal exposure to OVA (Fig. 1, c, m, and o). Furthermore, these mice showed a dose-dependent AHR to McH challenge (Fig. 2 A). In contrast, mice having received Th1 cells 30 d earlier showed significant cell infiltration composed mainly of lymphocytes and neutrophils after OVA administration (Fig. 1, g and h) but failed to respond to Mch challenge by AHR (Fig. 2 A). However, when they were nasally exposed to both Ag and IL-18, these mice increased their pathological changes characterized by massive cell infiltration (Fig. 1, i and j) and AHR (Fig. 2 A), suggesting that Ag and IL-18 stimulate Th1 cells to produce cytokines and chemokines that induce or enhance infiltration with eosinophils, lymphocytes, and neutrophils (Fig. 1, j). In contrast, mice that received Th1 or Th2 cells 30 d earlier showed neither lung inflammation (Fig. 1, e, f, k, and l) nor AHR (Fig. 2 A) after nasal exposure to PBS or IL-18, suggesting the contribution of Ag- or Ag plus IL-18–induced recall responses of memory Th2 or Th1 cells, respectively, to induction of bronchial asthma. Thus, Ag stimulation of memory Th1 cells induced airway inflammation without AHR, whereas Ag plus IL-18 stimulation induced both airway inflammation and AHR.


Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse.

Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K - J. Exp. Med. (2004)

IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. (A) AHR in response to increased concentrations of inhaled β-Mch was measured in a whole body plethysmograph. (B) Inflammatory cell composition of BALF from mice transferred with OVA-specific Th1 or Th2 cells and daily treated with intranasal administration of PBS or OVA and/or IL-18 consecutively for 3 d. Cell differential percentages were determined by light microscopic evaluation of cytospin preparation. Data are expressed as absolute numbers of cells. Representative results of five animals are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211833&req=5

fig2: IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. (A) AHR in response to increased concentrations of inhaled β-Mch was measured in a whole body plethysmograph. (B) Inflammatory cell composition of BALF from mice transferred with OVA-specific Th1 or Th2 cells and daily treated with intranasal administration of PBS or OVA and/or IL-18 consecutively for 3 d. Cell differential percentages were determined by light microscopic evaluation of cytospin preparation. Data are expressed as absolute numbers of cells. Representative results of five animals are shown.
Mentions: We established Th1 or Th2 cells by two rounds of 7-d stimulation of CD4+ T cells obtained from OVA-specific TCR Tg BALB/c (DO11.10) mice with OVA peptide, IL-12, and anti–IL-4 or with OVA peptide, IL-4, and anti–IL-12/anti–IFN-γ in the presence of APC for 2 wk, respectively. We then transferred these newly polarized Th1 or Th2 cells i.v. into normal BALB/c mice (107 per mouse) and allowed them to adopt a resting memory phenotype in vivo (51). 30 d after passive cell transfer, these recipients were daily treated with intranasal administration of OVA and/or IL-18 for 3 d. Therefore in this experimental system, we could depict the capacity of the memory-type Th1 or Th2 cells to induce bronchial asthma in naive mice. Histopathological analysis of the airways of each group of mice revealed that Th2 cell–transferred mice showed a significant increase in the peribronchial and perivenular infiltration with eosinophils and lymphocytes when compared with normal mice after nasal exposure to OVA (Fig. 1, c, m, and o). Furthermore, these mice showed a dose-dependent AHR to McH challenge (Fig. 2 A). In contrast, mice having received Th1 cells 30 d earlier showed significant cell infiltration composed mainly of lymphocytes and neutrophils after OVA administration (Fig. 1, g and h) but failed to respond to Mch challenge by AHR (Fig. 2 A). However, when they were nasally exposed to both Ag and IL-18, these mice increased their pathological changes characterized by massive cell infiltration (Fig. 1, i and j) and AHR (Fig. 2 A), suggesting that Ag and IL-18 stimulate Th1 cells to produce cytokines and chemokines that induce or enhance infiltration with eosinophils, lymphocytes, and neutrophils (Fig. 1, j). In contrast, mice that received Th1 or Th2 cells 30 d earlier showed neither lung inflammation (Fig. 1, e, f, k, and l) nor AHR (Fig. 2 A) after nasal exposure to PBS or IL-18, suggesting the contribution of Ag- or Ag plus IL-18–induced recall responses of memory Th2 or Th1 cells, respectively, to induction of bronchial asthma. Thus, Ag stimulation of memory Th1 cells induced airway inflammation without AHR, whereas Ag plus IL-18 stimulation induced both airway inflammation and AHR.

Bottom Line: Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18.Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro.Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, 663-8501, Japan.

ABSTRACT
Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-gamma production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

Show MeSH
Related in: MedlinePlus