Intrinsic AHR in IL-5 transgenic mice is dependent on CD4+ cells and CD49d-mediated signaling

Overexpression. of interleukin (IL)-5 by the airway epithelium in mice using the rat CC10 promoter (NJ.1726 line) leads to several histopathologies characteristic of human asthma, including airway hyperreactivity (AHR). We investigated the contribution of B and T cells, as well as CD4 expression, to the development of AHR in IL-5 transgenic mice. NJ.1726 mice on a T cell or CD4 knockout background, but not on a B cell knockout background, lost intrinsic AHR. These effects occurred without decreases in IL-5 or eosinophils. We further investigated the contribution Of alpha (4)-integrin signaling to the development of AHR in IL-5 transgenic mice through the administration of anti-CD49d (alpha (4)-integrin) antibody (PS/2). Administration of PS/2 resulted in immediate (16-h) inhibition of AHR. The inhibition of AHR was not associated with a decrease in airway eosinophils. These studies demonstrate that, despite the presence of increased levels of IL-5 and eosinophils in he lungs of NJ. 1726 mice, CD4(+) cells and alpha (4)-integrin signaling are necessary for the intrinsic AHR that develops in IL-5 transgenic mice.