The Pulmonary Host Defense System: of The Icos-Ligand B7-H2 Expression on Alveolar

The mechanism of immune defense against pathogens in the lung has so far been poorly understood. Here, we show that human type II alveolar epithelial cells play a key role in defense via interactions between B7 homolog (B7h), also known as ICOS ligand, and its receptor ICOS expressed on activated T cells. The A549 alveolar type II cell line abundantly expresses B7H2, CD40 and B7-1, but not B7-2 or hGL50. Tumor necrosis factor (TNF)-α significantly induced B7-H2 and CD40 expression by A549 cells, but had no effect on B7-1 or B7-2 expression. TNF-α-deficient mice exhibited low B7-H2 expression on alveolar epithelial cells in comparison with wild-type mice. Co-culture of TNF-α pre-stimulated A549 cells with CD4+ T cells promoted CD154 expression, CD4+ T cell proliferation and cytokine production, especially interferon (IFN)-α. Monocyte-derived TNF-α in combination with IFN-α and LPS markedly induced B7-H2 expression in A549 cells. This study thus identifies a unique co-stimulatory pathway via alveolar epithelial type II cells that preferentially affects CD4+ T helper cell function, implying that alveolar epithelial type II cells play a crucial role in innate immunity in the lung by regulating IFN-α-synthesis via B7-H2/ICOS interactions.