Regulatory T cells attenuate experimental periodontitis progression in mice.
OBJECTIVE
The aim of this study was to identify the presence and characterize the function of regulatory T cells (Tregs) in experimental periodontitis in mice.


METHODS
C57Bl/6 mice infected with Actinobacillus actinomycetemcomitans, treated or not with anti-glucocorticoid-inducible tumour necrosis factor receptor (anti-GITR) to inhibit Tregs function, were analysed regarding inflammatory cell and Tregs influx, alveolar bone loss and cytokine expression/production (analysed by real-time polymerase chain reaction and ELISA) throughout experimental periodontitis.


RESULTS
A. actinomycetemcomitans inoculation in mice resulted in periodontal disease characterized by marked alveolar bone loss and an influx of inflammatory cells. Flow cytometry evaluation of inflammatory cells demonstrated an increased number of CD4(+)CD25(+) and CD4(+)FOXp3(+) cells, characterizing the presence of Tregs in the periodontal environment in a late stage after infection. Tregs-associated cytokines interleukin-10 (IL-10), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) and transforming growth factor-beta (TGF-beta) were found to be expressed/produced in a kinetics that resembles Tregs migration. Treatment with anti-GITR, which inhibits Tregs function, showed increased alveolar bone loss and inflammatory cell migration. A reduction in IL-10, CTLA-4 and TGF-beta levels was also observed, while interferon-gamma, tumour necrosis factor-alpha and receptor activator for nuclear factor kappaB ligand levels were increased. However, bacterial load and C-reactive protein serum did not show any differences.


CONCLUSIONS
Taken together, our results showed that the presence of Treg cells attenuates the severity of experimental periodontitis without impairment in the control of infection.
Garlet
Gustavo P
GP
Department of Biological Sciences, School of Dentistry of Bauru, São Paulo University - FOB/USP, São Paulo, Brazil. garletgp@usp.br
Cardoso
Cristina R
CR
Mariano
Flavia S
FS
Claudino
Marcela
M
de Assis
Gerson F
GF
Campanelli
Ana P
AP
Avila-Campos
Mario J
MJ
Silva
João S
JS
D016976:Aggregatibacter actinomycetemcomitans; D016301:Alveolar Bone Loss / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D060908:CTLA-4 Antigen; D002634:Chemotaxis, Leukocyte; D055113:Chronic Periodontitis / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D053245:RANK Ligand; D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma