Dendritic cell involvement in pulmonary granuloma formation elicited by bacillus calmette-guérin in rats

Dendritic cells (DCs) are the most potent antigen-presenting cells that play a central role in initiating the primary immune response. However, their role in granulomatous inflammation has not been well studied. The aim of the present study was to elucidate the role of DCs in granuloma formation. Using a rat model of bacillus Calmette-Guérin (BCG)-elicited pulmonary granulomas, we investigated the distribution of DCs in the granulomas by immunohistochemistry with a rat-DC-specific monoclonal antibody, OX62. We found numerous large, pleiomorphic OX62(+) cells accumulating at the borders of the pulmonary granulomas. The OX62(+) cells isolated from the granulomatous lung showed intense surface expression of major histocompatibility complex class II, B7-1, and B7-2, and a lack of T cell- and monocyte/macrophage-specific markers. Their ultrastructural morphology was characteristic of DCs. Functionally, they had potent capacity to stimulate allogeneic T cells as well as purified protein derivative-specific syngeneic T cells in the absence of exogenous peptides. Based on these findings, the OX62(+) cells infiltrating the granulomas were considered to be DCs expressing BCG-derived peptides. These results indicate that DCs contribute to pulmonary granuloma formation elicited by BCG by means of their potent antigen-presenting function, providing a novel insight into DC function in T cell-mediated granulomatous immune responses.