The role of CD4+ T cells in periodontal disease

Campbell, Lauren Dee (2017) The role of CD4+ T cells in periodontal disease. PhD thesis, University of Glasgow.

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Abstract

Introduction: Periodontal disease (PD) is the most common bone destructive chronic inflammatory disease in humans. Severe PD affects 8-15% of the population and impacts on the ability to chew and appearance, reduces quality of life, and is responsible for a substantial proportion of dental care costs. A dysbiotic oral biofilm is necessary but insufficient for development of PD. Rather, a dysregulated immune response to the disease-associated biofilm results in destruction of tooth supporting structures and eventual tooth loss. Despite the apparent involvement of the immune system in PD, clinical management focuses solely on the mechanical removal of the oral biofilm – with partial success and frequent recurrence. Therefore, a better understanding of the immune response in PD could highlight potential novel preventative and therapeutic strategies. T cells are present at sites of PD; however, there remains ambiguity regarding whether these T cells are protective or destructive in PD. The aim of these studies was to characterize CD4+ T cells in a P. gingivalis-induced murine model of PD. Results: P. gingivalis-infected mice displayed subtle changes in their CD4+ T cell compartment, predominantly in the draining lymph nodes (dLNs). Such changes included a suggested increase in T follicular helper cells, a trend towards a decrease in regulatory T cells and a trend towards increased production of IFN-γ. Elevated levels of IFN-γ were also noted in gingival CD8+ T cells and splenocytes, with similar trends in CD8+ T cells from dLNs. The transcriptome of CD4+ T cells isolated from gingivae and dLNs of P. gingivalis–infected suggested minimal changes in gene expression following infection; however, identified a profile of the mucosal oral CD4+ T cell compared with CD4+ T cells of the dLN. To investigate the response of CD4+ T cells specific for P. gingivalis, the bacteria were genetically manipulated to express ovalubumin (OVA) peptide 323-339. However, these OVA peptide expressing P. gingivalis failed to induce a response in OVA-specific T cells, both in vitro and in vivo. Conclusion: These data imply that CD4+ T cells do not substantially change upon P. gingivalis infection in a murine model. IFN-γ production, however, was elevated both locally and systemically. Together, the data presented in this thesis and data previously published warrant further investigations into the role of IFN-γ in PD and may point to IFN-γ as a biomarker or biological target for adjunctive PD therapy.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: CD4+ T cells, T cells, periodontal disease, immunology, P. gingivalis, mucosa, IFN-γ.
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Funder's Name: UNSPECIFIED
Supervisor's Name: Culshaw, Dr. Shauna
Date of Award: 2017
Depositing User: Unnamed user with email l.campbell.3@research.gla.ac.uk
Unique ID: glathesis:2017-8241
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 07 Jun 2017 09:24
Last Modified: 04 Jul 2017 16:01
URI: http://theses.gla.ac.uk/id/eprint/8241

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