Cutting edge: MHC class II expression by pulmonary nonhematopoietic cells plays a critical role in controlling local inflammatory responses

The interaction of CD4⁺ T cells with MHC class II (MHCII)-expressing hematopoietic APCs plays a critical role in both the generation of protective immune responses and maintenance of tolerance in the lung. The functional significance of MHCII expression by nonhematopoietic stromal cells, however, has not been defined in vivo. Using a novel mouse model of orthotopic left lung transplantation, we demonstrate that selective elimination of MHCII expression on nonhematopoietic cells leads to an inflammatory response as a result of reduced peripheral generation of regulatory CD4⁺ T cells. Absence of MHCII expression on nonhematopoietic cells also inhibits local growth of metastatic pulmonary tumor. These findings indicate that nonhematopoietic cells play a previously unrecognized role in downregulating inflammatory responses in nonlymphoid tissues.