CD4+ T cells can induce airway hyperresponsiveness to allergen challenge in the brown norway rat

Am J Respir Crit Care Med. 1998 Dec;158(6):1863-70. doi: 10.1164/ajrccm.158.6.9709123.


Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4+ T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4+ T cells, CD8+ T cells, and a mixture of CD4+ and CD8+ T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4+ T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4+ and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4+ T cell recipients after OA challenge compared with other groups. Interferon-gamma mRNA was expressed to the greatest extent in CD8+ recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4+ T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8+ T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon-gamma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Allergens / immunology*
  • Animals
  • Bronchial Hyperreactivity / immunology*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoconstrictor Agents
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cattle
  • Eosinophilia / immunology
  • Gene Expression Regulation
  • Immunization
  • Immunoglobulin E / immunology
  • In Situ Hybridization
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology
  • Male
  • Methacholine Chloride
  • Ovalbumin / immunology
  • Proteins / analysis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred BN
  • Serum Albumin, Bovine / immunology
  • Time Factors


  • Aerosols
  • Allergens
  • Bronchoconstrictor Agents
  • Interleukin-5
  • Proteins
  • RNA, Messenger
  • Methacholine Chloride
  • Serum Albumin, Bovine
  • Immunoglobulin E
  • Interferon-gamma
  • Ovalbumin