Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation

J Clin Invest. 1999 Jan;103(2):175-83. doi: 10.1172/JCI5155.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allergens / immunology*
  • Animals
  • Asthma / immunology*
  • Bronchial Hyperreactivity / immunology*
  • Cytokines / immunology
  • Disease Models, Animal
  • Eosinophils / immunology
  • Histocytochemistry
  • Hypersensitivity / immunology
  • Inflammation / immunology*
  • Lung / pathology
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Allergens
  • Cytokines
  • Methacholine Chloride
  • Ovalbumin