Limits...
Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production.

Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly K - J. Exp. Med. (1997)

Bottom Line: When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells.These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes.These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

View Article: PubMed Central - PubMed

Affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lcohn@biomed.med.yale.edu

ABSTRACT
Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4-deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

Show MeSH

Related in: MedlinePlus

Bronchoalveolar lavage cell recovery in mice after transfer of  cells and exposure to inhaled OVA. Differential counts were performed  on cytospins of cells recovered from BAL from individual mice. Mean  cell counts (±SEM) are shown (n = 5 mice per group). One experiment  is shown and is representative of three experiments. Statistical significance  was determined by unpaired Student's t test. *P <0.0001 Th2 vs. Th1;  ‡P <0.02 Th1 vs. Th2.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199146&req=5

Figure 3: Bronchoalveolar lavage cell recovery in mice after transfer of cells and exposure to inhaled OVA. Differential counts were performed on cytospins of cells recovered from BAL from individual mice. Mean cell counts (±SEM) are shown (n = 5 mice per group). One experiment is shown and is representative of three experiments. Statistical significance was determined by unpaired Student's t test. *P <0.0001 Th2 vs. Th1; ‡P <0.02 Th1 vs. Th2.

Mentions: To investigate how different effector CD4 T cells influence inflammation in the respiratory tract, mice that received Th1, Th2, or unprimed naive CD4 T cells were compared. Mice that received Th1 or Th2 cells and were exposed to aerosolized OVA had moderate inflammation in the respiratory tract (Fig. 2, A1 and B1). The lungs from both groups of mice showed inflammation in a predominantly peribronchial and perivascular pattern. Despite similar degrees of inflammation, the two groups of mice had strikingly different inflammatory processes as determined by lung histology and analysis of BAL cells. The inflammatory infiltrates in the lungs of mice that received Th1 cells consisted of neutrophils, small mononuclear cells and macrophages (Fig. 2 B1). Differential counts performed on cells recovered from BAL confirmed these findings (Fig. 3). Immunohistochemical analysis of lung tissue showed that many infiltrating inflammatory cells stained with an anti-CD4 antibody (Fig. 4 A), the majority of these cells also stained with the TCR anticlonotypic antibody, KJ1-26 (Fig. 4 B). MHC Class II expression in the lungs of these mice was increased on bronchial epithelial cells (Fig. 4 C) when compared to mice that received Th2 cells (Fig. 4 D), as expected from the effects of IFN-γ on airway epithelial cells (42).


Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production.

Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly K - J. Exp. Med. (1997)

Bronchoalveolar lavage cell recovery in mice after transfer of  cells and exposure to inhaled OVA. Differential counts were performed  on cytospins of cells recovered from BAL from individual mice. Mean  cell counts (±SEM) are shown (n = 5 mice per group). One experiment  is shown and is representative of three experiments. Statistical significance  was determined by unpaired Student's t test. *P <0.0001 Th2 vs. Th1;  ‡P <0.02 Th1 vs. Th2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199146&req=5

Figure 3: Bronchoalveolar lavage cell recovery in mice after transfer of cells and exposure to inhaled OVA. Differential counts were performed on cytospins of cells recovered from BAL from individual mice. Mean cell counts (±SEM) are shown (n = 5 mice per group). One experiment is shown and is representative of three experiments. Statistical significance was determined by unpaired Student's t test. *P <0.0001 Th2 vs. Th1; ‡P <0.02 Th1 vs. Th2.
Mentions: To investigate how different effector CD4 T cells influence inflammation in the respiratory tract, mice that received Th1, Th2, or unprimed naive CD4 T cells were compared. Mice that received Th1 or Th2 cells and were exposed to aerosolized OVA had moderate inflammation in the respiratory tract (Fig. 2, A1 and B1). The lungs from both groups of mice showed inflammation in a predominantly peribronchial and perivascular pattern. Despite similar degrees of inflammation, the two groups of mice had strikingly different inflammatory processes as determined by lung histology and analysis of BAL cells. The inflammatory infiltrates in the lungs of mice that received Th1 cells consisted of neutrophils, small mononuclear cells and macrophages (Fig. 2 B1). Differential counts performed on cells recovered from BAL confirmed these findings (Fig. 3). Immunohistochemical analysis of lung tissue showed that many infiltrating inflammatory cells stained with an anti-CD4 antibody (Fig. 4 A), the majority of these cells also stained with the TCR anticlonotypic antibody, KJ1-26 (Fig. 4 B). MHC Class II expression in the lungs of these mice was increased on bronchial epithelial cells (Fig. 4 C) when compared to mice that received Th2 cells (Fig. 4 D), as expected from the effects of IFN-γ on airway epithelial cells (42).

Bottom Line: When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells.These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes.These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

View Article: PubMed Central - PubMed

Affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lcohn@biomed.med.yale.edu

ABSTRACT
Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4-deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

Show MeSH
Related in: MedlinePlus