Allergen-specific Th1 cells fail to counterbalance Th2 cell–induced airway hyperreactivity but cause severe airway inflammation
Gesine Hansen, … , Rosemarie H. DeKruyff, Dale T. Umetsu
Gesine Hansen, … , Rosemarie H. DeKruyff, Dale T. Umetsu
Published January 15, 1999
Citation Information: J Clin Invest. 1999;103(2):175-183. https://doi.org/10.1172/JCI5155.
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Article

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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Figure 7

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OVA-specific Th1 cells do not reduce airway hyperreactivity in OVA-immun...
OVA-specific Th1 cells do not reduce airway hyperreactivity in OVA-immunized BALB/c mice. BALB/c mice were immunized with OVA (50 μg) in alum intraperitoneally on days 0 and 14, and intranasally (50 μg OVA in 50 μl PBS) on days 14, 25, 26, and 27 (OVA; n = 6). A second group of mice also received OVA-specific Th1 cells intravenously on days 14 and 25 (2.5 × 106 cells per mouse at each time point) (OVA + Th1; n = 5). Control mice received alum intraperitoneally and PBS intranasally (no antigen; n = 6). Airway hyperreactivity to methacholine was determined as in Figs. 5 and 6. Results are expressed as mean ± SEM. Transfer of Th1 cells without administration of antigen did not have any effect on airway hyperreactivity (data not shown).