Effect of α₄-integrin blockade on CD4⁺ late airway responses in the rat

The blockade of α₄ integrins with a monoclonal antibody (TA-2) decreases late airway responses (LR) in ovalbumin (OVA)-sensitized and challenged rats. In this study, we used a model of CD4⁺ cell-driven LR to test the hypothesis that α₄-integrin blockade involves interference with T-cell activation in the inhibition of LR. Purified CD4⁺ cells from OVA-sensitized rats were transferred to unsensitized recipients, which received either TA-2 or a control antibody (cAb), and were OVA-challenged. A sham-challenged group was also studied. LR, calculated from pulmonary resistance after challenge, were reduced in the TA-2 group compared with the cAb group (p = 0.015). Total cell counts, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL), and CD3⁺ cells in airway sections, were unaffected. The cab group had higher numbers of cells expressing interleukin-5 (IL-5) mRNA (55.2 ± 3.39 cells/1,000, mean ± SEM) and major basic protein (MBP) (6.2 ± 0.4/100 cells) in bronchoalveolar lavage (BAL), than the TA-2 group (25.37 ± 2.41 IL-5⁺ and 2.7 ± 0.2 MBP⁺) and the sham group (12.37 ± 0.96 IL-5⁺, 1.7 ± 0.1 MBP⁺). Interferon gamma (IFN-γ) mRNA⁺ cells were downregulated in both OVA-challenged groups, compared with the sham group. Our results suggest that the attenuation of LR and eosinophilia by σ₄-integrin blockade may involve interference with CD4⁺ cell activation and IL-5 expression.