Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies.
Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal 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 epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, 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 higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.
Jotwani
R
R
Department of Periodontics, School of Dental Medicine, State University of New York, Stony Brook, NY 11794, USA.
Palucka
A K
AK
Al-Quotub
M
M
Nouri-Shirazi
M
M
Kim
J
J
Bell
D
D
Banchereau
J
J
Cutler
C W
CW
D000328:Adult; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002465:Cell Movement; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000166:cytology*; D005881:Gingiva / Q000166:cytology; D005883:Gingival Crevicular Fluid / Q000276:immunology; D005891:Gingivitis / Q000276:immunology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008221:Lymphoid Tissue / Q000254:growth & development; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D018448:Models, Immunological; D009061:Mouth Mucosa / Q000166:cytology* / Q000276:immunology; D010518:Periodontitis / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen