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T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production.

Cohn L, Homer RJ, Niu N, Bottomly K - J. Exp. Med. (1999)

Bottom Line: and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-gamma?In the absence of IFN-gamma receptor signaling, Th1 cells induced mucus but not eosinophilia.Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-gamma.

View Article: PubMed Central - PubMed

Affiliation: Section of Pulmonary Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lauren.cohn@yale.edu

ABSTRACT
CD4 T helper (Th) type 1 and Th2 cells have been identified in the airways of asthmatic patients. Th2 cells are believed to contribute to pathogenesis of the disease, but the role of Th1 cells is not well defined. In a mouse model, we previously reported that transferred T cell receptor-transgenic Th2 cells activated in the respiratory tract led to airway inflammation with many of the pathologic features of asthma, including airway eosinophilia and mucus production. Th1 cells caused inflammation with none of the pathology associated with asthma. In this report, we investigate the role of Th1 cells in regulating airway inflammation. When Th1 and Th2 cells are transferred together into recipient mice, there is a marked reduction in airway eosinophilia and mucus staining. To address the precise role of Th1 cells, we asked (i), Are Th2-induced responses inhibited by interferon (IFN)-gamma? and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-gamma? In IFN-gamma receptor(-/-) recipient mice exposed to inhaled antigen, the inhibitory effects of Th1 cells on both airway eosinophilia and mucus production were abolished. In the absence of IFN-gamma receptor signaling, Th1 cells induced mucus but not eosinophilia. Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-gamma. The blockade of eosinophilia and mucus production by IFN-gamma likely occurs through different inhibitory pathways that are activated downstream of Th2 cytokine secretion and require IFN-gamma signaling in tissue of recipient mice.

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Effects of Th1 cells on airway eosinophilia. Th1, Th2, or Th1 + Th2 cells (numbers shown) were transferred into BALB/c recipient mice, and mice were exposed to inhaled OVA for 7 d. 24 h later, mice were killed and BAL was performed. Total cell and differential counts were performed on cells recovered from BAL in individual mice. Data represents mean number of BAL eosinophils (±SEM) (n = 4 mice per group). One experiment is shown and is representative of four experiments. Statistical significance was determined by unpaired Student's t test. *P < 0.05 Th2 versus Th1 (1.25) + Th2 (2.5); ‡P < 0.002 Th2 versus Th1 (2.5) + Th2 (2.5).
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Figure 2: Effects of Th1 cells on airway eosinophilia. Th1, Th2, or Th1 + Th2 cells (numbers shown) were transferred into BALB/c recipient mice, and mice were exposed to inhaled OVA for 7 d. 24 h later, mice were killed and BAL was performed. Total cell and differential counts were performed on cells recovered from BAL in individual mice. Data represents mean number of BAL eosinophils (±SEM) (n = 4 mice per group). One experiment is shown and is representative of four experiments. Statistical significance was determined by unpaired Student's t test. *P < 0.05 Th2 versus Th1 (1.25) + Th2 (2.5); ‡P < 0.002 Th2 versus Th1 (2.5) + Th2 (2.5).

Mentions: Mice received transfer of Th1, Th2, or a mixture of Th1 and Th2 cells (Th1 + Th2) and were exposed to inhaled antigen. Airway eosinophilia, which is consistently present after transfer of Th2 cells and exposure to inhaled OVA, is markedly reduced when Th1 + Th2 cells are transferred (Fig. 2). The inhibitory effects of Th1 cells on airway eosinophilia are dependent on the number of Th1 cells transferred, as when fewer Th1 cells are transferred into the mice, more eosinophils are present in the BAL. When equal numbers of Th1 and Th2 cells were transferred together and mice were exposed to inhaled antigen, eosinophils were consistently inhibited sevenfold or greater in experiments that employed transfer of a range of different cell numbers (106–5 × 106 cells). Mice exposed to inhaled OVA after no cells were transferred or after Th1 cells were transferred did not exhibit BAL eosinophilia.


T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production.

Cohn L, Homer RJ, Niu N, Bottomly K - J. Exp. Med. (1999)

Effects of Th1 cells on airway eosinophilia. Th1, Th2, or Th1 + Th2 cells (numbers shown) were transferred into BALB/c recipient mice, and mice were exposed to inhaled OVA for 7 d. 24 h later, mice were killed and BAL was performed. Total cell and differential counts were performed on cells recovered from BAL in individual mice. Data represents mean number of BAL eosinophils (±SEM) (n = 4 mice per group). One experiment is shown and is representative of four experiments. Statistical significance was determined by unpaired Student's t test. *P < 0.05 Th2 versus Th1 (1.25) + Th2 (2.5); ‡P < 0.002 Th2 versus Th1 (2.5) + Th2 (2.5).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195688&req=5

Figure 2: Effects of Th1 cells on airway eosinophilia. Th1, Th2, or Th1 + Th2 cells (numbers shown) were transferred into BALB/c recipient mice, and mice were exposed to inhaled OVA for 7 d. 24 h later, mice were killed and BAL was performed. Total cell and differential counts were performed on cells recovered from BAL in individual mice. Data represents mean number of BAL eosinophils (±SEM) (n = 4 mice per group). One experiment is shown and is representative of four experiments. Statistical significance was determined by unpaired Student's t test. *P < 0.05 Th2 versus Th1 (1.25) + Th2 (2.5); ‡P < 0.002 Th2 versus Th1 (2.5) + Th2 (2.5).
Mentions: Mice received transfer of Th1, Th2, or a mixture of Th1 and Th2 cells (Th1 + Th2) and were exposed to inhaled antigen. Airway eosinophilia, which is consistently present after transfer of Th2 cells and exposure to inhaled OVA, is markedly reduced when Th1 + Th2 cells are transferred (Fig. 2). The inhibitory effects of Th1 cells on airway eosinophilia are dependent on the number of Th1 cells transferred, as when fewer Th1 cells are transferred into the mice, more eosinophils are present in the BAL. When equal numbers of Th1 and Th2 cells were transferred together and mice were exposed to inhaled antigen, eosinophils were consistently inhibited sevenfold or greater in experiments that employed transfer of a range of different cell numbers (106–5 × 106 cells). Mice exposed to inhaled OVA after no cells were transferred or after Th1 cells were transferred did not exhibit BAL eosinophilia.

Bottom Line: and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-gamma?In the absence of IFN-gamma receptor signaling, Th1 cells induced mucus but not eosinophilia.Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-gamma.

View Article: PubMed Central - PubMed

Affiliation: Section of Pulmonary Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. lauren.cohn@yale.edu

ABSTRACT
CD4 T helper (Th) type 1 and Th2 cells have been identified in the airways of asthmatic patients. Th2 cells are believed to contribute to pathogenesis of the disease, but the role of Th1 cells is not well defined. In a mouse model, we previously reported that transferred T cell receptor-transgenic Th2 cells activated in the respiratory tract led to airway inflammation with many of the pathologic features of asthma, including airway eosinophilia and mucus production. Th1 cells caused inflammation with none of the pathology associated with asthma. In this report, we investigate the role of Th1 cells in regulating airway inflammation. When Th1 and Th2 cells are transferred together into recipient mice, there is a marked reduction in airway eosinophilia and mucus staining. To address the precise role of Th1 cells, we asked (i), Are Th2-induced responses inhibited by interferon (IFN)-gamma? and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-gamma? In IFN-gamma receptor(-/-) recipient mice exposed to inhaled antigen, the inhibitory effects of Th1 cells on both airway eosinophilia and mucus production were abolished. In the absence of IFN-gamma receptor signaling, Th1 cells induced mucus but not eosinophilia. Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-gamma. The blockade of eosinophilia and mucus production by IFN-gamma likely occurs through different inhibitory pathways that are activated downstream of Th2 cytokine secretion and require IFN-gamma signaling in tissue of recipient mice.

Show MeSH
Related in: MedlinePlus