The ICOS-ligand B7-H2, expressed on human type II alveolar epithelial cells, plays a role in the pulmonary host defense system.

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 B7-H2, CD40 and B7-1, but not B7-2 or hGL50. 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 IFN-γ. Monocyte-derived TNF-α in combination with IFN-γ and LPS markedly induced B7-H2 expression in A549 cells. This study thus identifies a unique costimulatory pathway via alveolar epithelial type II cells that preferentially affects T helper cell function, implying that alveolar epithelial type II cells play a crucial role in innate immunity in the lung by regulating IFN-γ-synthesis via B7-H2/ICOS interactions.