Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells.

Abstract

SummaryWe have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4 + T cells and interleukin 5. To determine whether interferon 3' ) regulates antigen-induced eosinophll recruitment into the tissue, we studied the effect of recombinant (r) murine IFN-3, and of anti-IFN-3, monoclonal antibody (mAb) on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. The intraperitoneal administration of rlFN-3, prevented antigen-induced eosinophil infiltration in the trachea of sensitized mice. The administration of rIFN-3, also decreased antigen-induced CD4 + T cell but not CD8 + T cell infiltration in the trachea. On the other hand, pretreatment with anti-IFN-'y mAb enhanced antigen-induced eosinophil and CD4 + T cell infiltration in the trachea. These results indicate that IFN-3, regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4 + T cell infiltration. Eosinophil infiltrate is a characteristic feature of allergic inflammation such as asthma. In a murine model of airway late-phase reaction, we have previously shown that antigeninduced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4 + T cells and IL-5 (1). However, the mechanism that regulates antigen-induced eosinophil recruitment into the tissue is unknown. It has been suggested that CD4 + Th cells can be divided into two subsets (Thl and Th2 cells) on the basis of their different patterns of cytokine secretion (2); Thl cells produce Ib2, IFN-3,, and lymphotoxin, and Th2 cells produce Ib4, IL-5, and Ib6. Furthermore, IFN-3, has been shown to be a major regulatory cytokine that inhibits the proliferation of Th2 cells in vitro (3, 4) and antagonizes the in vivo Th2-type responses such as IL-4-dependent IgE antibody production (5). Therefore, to determine whether IFN-3, regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of recombinant murine IFN-3' and of anti-IFN-3, mAb on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. Our results indicate that IFN-3, regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4 § T cell infiltration. Materials and Methods Mice and Immunization. 8-wk-old BALB/c mice (Charles RiverLaboratories, Shizuoka, Japan) were immunized intraperitoneally twice with 1 #g of OVA (Sigma Chemical Co., St. Louis, MO) in 4 mg of aluminum hydroxide at a 2-wk interval. 10-14 d after the second immunization, the sensitized mice were challenged with aerosolized OVA as described below. Antigen-induced Eosinophil lnfihration in Mouse Trachea.The eosinophil infiltration into the trachea was induced by the inhalation of antigen in sensitized mice, and the number of eosinophils infiltrating into the submucosal tissue of trachea was evaluated as described previously (1). Briefly, the sensitized mice inhaled aerosolized OVA (50 mg/ml) dissolved in 0.9% saline by a nebulizer (646; DeVilbiss Corp., Somerset, PA) for 20 min. As a...

The role of interferon-gamma on immune and allergic responses

“…It has been demonstrated that Th1 lymphocytes and cytokines such as IFN-γ and IL-12 may counteract and suppress Th2 responses of allergic diseases (Iwamoto et al 1993, Cohn et al 1999, Dow et al 1999. In fact, defective IFN-γ production predisposes toward the development of allergic diseases, and patients with severe asthma present significantly reduced IFN-γ production in response to allergen when compared to control individuals (Leonard et al 1997, Renzi et al 1999.…”

“…In vivo models of allergic inflammation have also proved the properties of IFN-γ to regulate allergen-induced eosinophilic infiltration. Recombinant IFN-γ treatment before inhalation of aerosolized antigen prevented eosinophil infiltration into the trachea of sensitized mice (Iwamoto et al 1993). Targeted disruption of the IFN-γ receptor gene has resulted in a prolonged airway eosinophilia in response to allergen, suggesting that IFN-γ signaling pathway is crucial to control eosinophil recruitment in vivo (Coyle et al 1996).…”

Bacterial Lipopolysaccharide Signaling Through Toll-Like Receptor 4 Suppresses Asthma-Like Responses Via Nitric Oxide Synthase 2 Activity

“…10). The beneficial effects of LPS are thought to be mediated by enhanced secretion of the type 1 cytokines IL-12 and IFN-␥ that are known to down-modulate allergic responses (11,12). Conversely, airborne LPS might adversely affect asthmatics by enhancing an established airway inflammation and airway obstruction (13,14).…”

Relationship between cytokine expression patterns and clinical outcomes: two population‐based birth cohorts

“…The IL‐13 and IFN‐γ coexpressors (Class 2) showed much lower risks for HDM sensitization compared to Class 3, where the majority did not express IFN‐γ. In the sensitization model, mice receiving recombinant IFN‐γ or intravenous IFN‐γ gene showed reduced antigen‐induced eosinophillic airway infiltration and inhibited development of AHR, suggesting a possible protective role for IFN‐γ 44, 45.…”