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Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown–Norway rats

By T-J Huang, P A Macary, D M Kemeny and K F Chung


We examined the role of CD8+ T cells in a Brown–Norway rat model of asthma, using a monoclonal antibody to deplete CD8+ T cells. Ovalbumin (OA)-sensitized animals were given anti-CD8 antibody (0·5 mg/rat) intravenously 1 week prior to exposure to 1% OA aerosol and were studied 18–24 hr after aerosol exposure. Following administration of anti-CD8 antibody, CD8+ cells were reduced to <1% of total lymphocytes in whole blood and in spleen. In sensitized animals, OA exposure induced bronchial hyper-responsiveness (BHR), accumulation of eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also an increase in tissue eosinophils and CD2+, CD4+ and CD8+T cells in airways. Anti-CD8 antibody caused a further increase in allergen-induced BHR (P < 0·03, compared with sham-treated animals), together with a significant increase in eosinophil number in BAL fluid (P < 0·05). While CD2+ and CD4+ T cells in airways were not affected by anti-CD8 treatment, the level of CD8+ T cells was significantly reduced in sensitized, saline-exposed animals (P < 0·04, compared with sham-treated rats), and sensitized and OA-challenged rats (P < 0·002, compared with sham-treated rats). Using reverse transcription–polymerase chain reaction, an increase of T helper (Th)2 cytokine [interleukin (IL)-4 and IL-5], and also of Th1 cytokine [interferon-γ (IFN-γ) and IL-2], mRNA in the lung of sensitized and OA-exposed animals was found; after CD8+ T-cell depletion, Th1 cytokine expression was significantly reduced (P < 0·02), while Th2 cytokine expression was unchanged. CD8+ T cells have a protective role in allergen-induced BHR and eosinophilic inflammation, probably through activation of the Th1 cytokine response

Topics: Original Articles
Publisher: Blackwell Science Inc
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Provided by: PubMed Central
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