Cloned Th cells confer eosinophilic inflammation and bronchial hyperresponsiveness.
BACKGROUND
The essential role of Th cells and T cell cytokines in eosinophilic inflammation has been established.


METHODS
To determine whether Th cells are sufficient for the development of airway eosinophilic inflammation, ovalbumin-reactive murine Th clones were established and infused into unprimed mice.


RESULTS
Eosinophilic infiltration into the lung was induced upon antigen inhalation in parallel with the rise in bronchoalveolar lavage fluid (BALF) eosinophil peroxidase activity. Neither IgG, IgA, nor IgE antibodies were present in this model. Pathological examination showed swelling and desquamation of epithelial cells, mucous plugs, and goblet cell hyperplasia, all of which well resemble human asthma. Fluorescent probe labeled Th clones migrated into the lung prior to the eosinophil accumulation. Bronchial hyperresponsiveness (BHR) was clearly induced upon antigen inhalation. Anti-IL-5 monoclonal antibody abrogated the responses. Dexamethasone and cyclosporin A suppressed cytokine production by Th cells both in vitro and in vivo, BALF eosinophilia, and BHR. The number of eosinophils recovered in the BALF correlated with the intensity of BHR.


CONCLUSIONS
The results clearly indicated that monoclonal Th cells are sufficient for the development of both airway eosinophilia and BHR. Agents capable of downregulating IL-5 production seem promising for the treatment of bronchial asthma.
Kaminuma
O
O
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan. osamu@liai.org
Mori
A
A
Ogawa
K
K
Nakata
A
A
Kikkawa
H
H
Ikezawa
K
K
Okudaira
H
H
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*