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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/L862    most recent 00516.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Pierce, J. Articles by Tesfaigzi, Y. Search for Related Content PubMed PubMed Citation Articles by Pierce, J. Articles by Tesfaigzi, Y.

Loss of pro-apoptotic Bim promotes accumulation of pulmonary T lymphocytes and enhances allergen-induced goblet cell metaplasia

¹Lovelace Respiratory Research Institute, Albuquerque, New Mexico; and ²The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Submitted 7 December 2005 ; accepted in final form 25 May 2006

Immunological tolerance during prolonged exposure to allergen is accompanied by a shift in the lymphocyte content and a reduction of goblet cell metaplasia (GCM). Bim initiates negative selection of autoreactive T and B cells and shut down of T cell immune responses in vivo. The present study investigated whether Bim plays a role in the resolution of GCM during prolonged exposure to allergen. Loss of Bim increased T lymphocyte numbers in the bronchoalveolar lavage at 4 and 15 days of allergen exposure. The numbers of pulmonary CD4⁺8^–, CD4^–8⁺, and T cells were significantly higher in naive and allergen-challenged bim^–/– mice compared with wild-type (WT) littermates. When activated, pulmonary bim^–/– T cells produced increased levels of IFN compared with bim^+/+ T cells. No differences were noted in the total numbers of epithelial cells per millimeter of basal lamina between bim^+/+ and bim^–/– mice, and the rate of resolution over 15 days of exposure was similar in both groups of mice. However, GCM was significantly enhanced and expression of IL-13R2 was reduced in bim^–/– mice compared with WT mice at 4 days. Furthermore, treatment of bronchiolar explant cultures with increasing IFN levels reduced immunostaining for IL-13R2. Collectively, these studies suggest that, during prolonged exposure to allergen, Bim plays no role in the resolution of GCM, but increased IFN levels in bim^–/– mice may be responsible for reduced expression of IL-13R2 and enhanced GCM despite similar levels of IL-13 in bim^+/+ and bim^–/– mice.

asthma; interferon- and tolerance; apoptosis; IL-13R2; mucous cell metaplasia

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