Adoptively transferred late allergic response is inhibited by IL-4, but not IL-5, antisense oligonucleotide

Abstract

Background: We have shown previously that the late airways response (LAR) can be transferred by ovalbumin-primed CD4 + T lymphocytes in Brown Norway rats. This response is associated with an increase of eosinophils and high expression of T H2 cytokines (IL-4 and IL-5) in bronchoalveolar lavage (BAL) fluid. Objective: In this study we hypothesized that the inhibition of IL-4 or IL-5 production in the CD4 + cells transferred to a naive animal could decrease the LAR and prevent airway eosinophilia in response to antigen challenge. Methods: CD4 + cells, purified from the cervical lymph nodes of ovalbumin-sensitized rats, were maintained in culture for 6 hours with medium alone or with 10 μg/mL IL-4 antisense (AS), IL-5 AS, or control AS oligodeoxynucleotide. Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol. The lung resistance was measured for 8 hours, and then BAL was performed. Cytospin preparations from BAL cells were assessed for the presence of eosinophils by immunocytochemistry for major basic protein and for IL-4, IL-5, and IFN-γ expression. Results: In rats injected with IL-4 AS–treated T cells, LAR, eosinophils, and IL-4 and IL-5 expression were significantly decreased compared with the other groups. Only IL-5 expression in BAL fluid was slightly decreased consequent to the transfer of IL-5 AS–treated T cells. Conclusion: This study demonstrates that, in the CD4 + T cell–driven LAR, the early production of IL-4, but not IL-5, by the transferred CD4 + cells is essential for the development of the LAR. (J Allergy Clin Immunol 1999;104:205-14.)