Effect of alpha(4)-integrin blockade on CD4(+) cell-driven late airway responses in the rat

The blockade of alpha (4) integrins with a monoclonal antibody (TA-2) decre ases late airway responses (LR) in ovalbumin (OVA)-sensitized and challenge d rats. In this study, we used a model of CD4(+) cell-driven LR to test the hypothesis that alpha (4)-integrin blockade involves interference with T-c ell activation in the inhibition of LR. Purified CD4+ cells from OVA-sensit ized rats were transferred to unsensitized recipients, which received eithe r TA-2 or a control antibody (cAb), and were OVA-challenged. A sham-challen ged 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, neutrophits, and lymphocytes in bro nchoalveolar lavage (BAL), and CD3(+) cells in airway sections, were unaffe cted. The cAb group had higher numbers of cells expressing interleukin-5 (I L-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-gamma) mRN A(+) cells were downregulated in both OVA-challenged groups, compared with the sham group. Our results suggest that the attenuation of LR and eosinoph ilia by alpha (4)-integrin blockade may involve interference with CD4(+) ce ll activation and IL-5 expression.