CD4+ T cells can induce airway hyperresponsiveness to allergen challenge in the brown norway rat.
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.
Mishima
H
H
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada.
Hojo
M
M
Watanabe
A
A
Hamid
Q A
QA
Martin
J G
JG
D000336:Aerosols; D000485:Allergens / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016085:Bronchoconstrictor Agents; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D004802:Eosinophilia / Q000276:immunology; D005786:Gene Expression Regulation; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride; D010047:Ovalbumin / Q000276:immunology; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D012710:Serum Albumin, Bovine / Q000276:immunology; D013997:Time Factors
D000336:Aerosols; D000485:Allergens; D016085:Bronchoconstrictor Agents; D015848:Interleukin-5; D011506:Proteins; D012333:RNA, Messenger; D016210:Methacholine Chloride; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin