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

Background: We have shown previously that the late airways response (LAR) c an 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 decrea se 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 o r with 10 mu g/mL IL-4 antisense (AS), IL-5 AS, or control AS oligodeoxynuc leotide. Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol, The lung res istance was measured for 8 hours, and then BAL was performed. Cytospin prep arations from BAL cells were assessed for the presence of eosinophils by im munocytochemistry for major basic protein and for IL-4, IL-5, and IFN-gamma expression. Results: In rats injected with IL-4 AS-treated T cells, LAR, eosinophils, a nd IL-4 and IL-5 expression were significantly decreased compared with the other groups. Only IL-5 expression in BAL fluid was slightly decreased cons equent 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.