Mature dendritic cells infiltrate the T cell-rich region of oral mucosa inchronic periodontitis: In situ, in vivo, and in vitro studies

Previous studies have analyzed the lymphoid and myeloid foci within the gin gival mucosa in health and chronic periodontitis (CP); however, the princip al APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a() immature Langerhans cells predominantly infiltrate the gingival epitheliu m, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbat ion of CP results In increased levels of proinflammatory cytokines that med iate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated mono cyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflam matory (IL-1 beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold hig her than that from Escherichia coli-pulsed DCs. This may account for the si gnificantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken t ogether, these findings suggest a previously unreported mechanism for the p athophysiology of CP, involving the activation and in situ maturation of DC s by the oral pathogen A gingivalis, leading to release of counterregulator y cytokines and the formation of T cell-DC foci.