Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 1123-1131

CD8 Depletion-induced Late Airway Response Is Characterized by Eosinophilia, Increased Eotaxin, and Decreased IFN- Expression in Rats

ZOULFIA ALLAKHVERDI, BOUCHAIB LAMKHIOUED, RONALD OLIVENSTEIN, QUTAYBA HAMID, and PAOLO M. RENZI

CHUM Research Center, Notre-Dame Hospital, University of Montreal, and Meakins-Christie Laboratories and Department of Medicine and Pathology, McGill University, Montreal, Quebec, Canada

There is an emerging body of knowledge defining the role of CD8⁺ cells in the pathogenesis of allergic asthma. We have previously demonstrated in sensitized Sprague-Dawley (SD) rats that depletion of CD8⁺ cells caused an increase in the late airway response (LAR) and cellular infiltration after antigen challenge. To better delineate the mechanism of CD8⁺ cell involvement in the development of the LAR and airway inflammation, we investigated the pattern of chemokine and cytokine production after antigen challenge. SD rats were sensitized to ovalbumin (OA) and subsequently treated with anti-CD8 (OX-8) monoclonal antibody (mAb) for the depletion of CD8⁺ cells or with control mouse anti-rat IgG₁ mAb as a control procedure. After OA challenge, CD8- depleted SD rats developed an increased LAR when compared with control rats (area under the curve: 16.65 ± 6.6 in CD8- depleted rats versus 5.39 ± 2.0 in control animals; p < 0.05). Compared with the control animals, the increase in the LAR was accompanied by a significantly increased eosinophilic infiltration of the airways and was associated with increased eotaxin expression (both messenger RNA [mRNA] and protein) in the CD8-depleted group. There were no differences between the groups in RANTES or monocyte chemoattractant protein-1 (MCP-1) expression. In addition, we found a significantly lower interferon gamma (IFN-) mRNA expression in the CD8-depleted rats, without any effects on interleukin (IL)-4 and IL-5 mRNA expression when measured either by semiquantitative reverse transcriptase/polymerase chain reaction (RT-PCR) or by in situ hybridization for the number of cells expressing these cytokines. Taken together, these results suggest that CD8⁺ cells from sensitized SD rats exhibit the functional capacity to suppress the LAR, possibly through downregulation of eotaxin expression and increased expression of IFN- mRNA.

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