Allergen-specific Th1 cells fail to counterbalance Th2 cell–induced airway hyperreactivity but cause severe airway inflammation
Gesine Hansen, Gerald Berry, Rosemarie H. DeKruyff, Dale T. Umetsu
Gesine Hansen, Gerald Berry, Rosemarie H. DeKruyff, Dale T. Umetsu
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Allergen-specific Th1 cells fail to counterbalance Th2 cell–induced airway hyperreactivity but cause severe airway inflammation

Abstract

Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell–induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.

Authors

Gesine Hansen, Gerald Berry, Rosemarie H. DeKruyff, Dale T. Umetsu

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Histologic examination of lungs from SCID mice receiving Th1, Th2, and T...
Histologic examination of lungs from SCID mice receiving Th1, Th2, and Th0 cells. (a) Lung tissue from control SCID mouse that received intranasal OVA but no Th cells. H&E, ×250. Inset: High-power magnification of normal bronchiolar epithelium. H&E, ×400. (b) Lung tissue from SCID mouse that received Th2 cells and intranasal OVA. Peribronchiolar mononuclear cell infiltrates are noted. The airway lumen is filled and expanded by thick mucus. H&E, ×250. Inset: High-power magnification of the airway epithelium showing tall columnar cells exhibiting abundant cytoplasmic mucin and a collarette of inflammatory cells. H&E, ×400. (c) Lung tissue from SCID mouse that received Th1 cells and intranasal OVA. Dense peribronchiolar inflammatory infiltrates are seen. The airway lumen does not contain mucus plugs. H&E, ×250. Inset: Lymphocytes are penetrating the airway epithelium and surrounding tissue spaces. H&E, ×400. (d) Lung tissue from control SCID mouse that received Th1 cells but not intranasal OVA. The bronchiole is normal with rare mononuclear cells in the peribronchiolar tissue; H&E ×250. Inset: The airway epithelium is normal. H&E, ×400. (e) Lung tissue from SCID mouse that received Th0 cells and intranasal OVA. Peribronchiolar infiltrates are noted, and the lumen is filled with mucus; scattered inflammatory cells are noted. H&E, ×250. Inset: The airway epithelium resembles that of mice that received OVA-specific Th2 cells, with the presence of tall columnar cells with abundant cytoplasmic mucin (b). (f) Lung tissue from SCID mouse that received both Th1 and Th2 cells and intranasal OVA. Significant airway inflammation is noted, without airway mucus. H&E, ×250. Inset: The epithelium displays reactive-appearing columnar cells, with inflammatory cells at the bases. H&E, ×400. H&E, hematoxylin and eosin; SCID, severe combined immunodeficiency.