Cytokine Profiles of T-lymphocytes from Gingival Tissues with Pathological Pocketing

Abstract

Periodontal disease is an infection in which destruction occurs at sites remote from the infection, resulting in pathological pocketing. Intervening between the infection and the destruction is a dense mononuclear inflammatory infiltrate. It has been suggested that this infiltrate might have characteristics and the destructive potential of Th1-type T lymphocytes. To ascertain the nature of the infiltrates we investigated the expression of mRNA for IL-2, IL-5, and IFN-gamma by gingival mononuclear cells (GMC) from healthy (n = 8) or adult periodontitis (AP) patients (n = 25) by using cytokine-specific reverse-transcription/polymerase-chain-reaction (RT-PCR). GMC, as obtained from patients' tissues, expressed IL-2, IFN-gamma, or IL-5 mRNA. Significantly higher proportions of GMC from AP patients expressed IL-2 and IFN-gamma mRNA than did those from healthy subjects. IFN-gamma was the most consistent cytokine message detected. In other experiments, gingival T-lymphocytes (n = 12) and CD4+ and CD8+ gingival T-lymphocytes (n = 16) were isolated from gingival tissues removed surgically from AP patients. AP gingival T-lymphocytes expressed mRNA for IL-2, IFN-gamma, or IL-6 prior to stimulation. After stimulation with Con A, the cells significantly up-regulated IL-5 and IL-6 message expression. Both CD4+ and CD8+ gingival T-lymphocytes expressed IFN-gamma, IL-5, and some IL-2. This cumulative cytokine profile observed in these experiments is consistent with the predominance of Th1-type cells in pathological tissues and with Th2-type cells, which can also be present, being up-regulated under appropriate stimulation. Importantly, CD4+ and CD8+ lymphocytes were shown to express T1- and T2-type cytokine message, emphasizing the potential for CD8+ T-lymphocytes to participate in periodontal disease pathology.

Th1 biased response to a novel Porphyromonas gingivalis protein aggravates bone resorption caused by this oral pathogen

“…We and others have shown that infection with live P. gingivalis predominantly elicits a Th1-type response in experimental animals and in humans [15]. In addition, adoptive transfer experiments have indicated an active role for Th1 cytokines in periodontal disease exacerbation, and some studies have shown that Th2 cytokines may be protective [9,16]. However, other studies suggest that this association is not consistently observed [17,18,19].…”

“…In all of these models, infection with P. gingivalis elicits a cell-mediated Th1 type response characterized by increased production of IFN-γ, IL-12 and TNFα, and leads to increased inflammation and bone destruction [5,6]. Similarly, high levels of Th1 cytokines in gingival tissues and mononuclear cells, and gingival crevicular fluid are associated with increased periodontal disease progression [7,8,9]. We recently showed that dental pulp infection with P. gingivalis causes extensive inflammation and bone destruction and is associated with a strong Th1 response, characterized by increased intra-lesional production of IFNγ and IL-1 [6].…”

TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

“…9 The Th1-polarized immune responses have long been implicated in the pathogenesis of periodontal diseases, since their characteristic cytokine products are overexpressed in the diseased tissues and in mononuclear cells isolated from periodontitis patients. 10 Also, from a mechanistic viewpoint, the prototypic Th1-cytokine IFN-g amplify and exacerbate the pro-inflammatory activity of infiltrating phagocytes and resident cells, ultimately increasing matrix metalloproteinase (MMP) and receptor activator of NFkB ligand (RANKL) levels, leading to augmented tissue destruction. [11][12][13] While recent evidence points to the participation of other T helper subsets (such as Th17 and Thf) in the pathogenesis of osteolytic inflammatory lesions, numerous studies demonstrate that the Th1 subset can be independently responsible for the establishment and progression of periodontitis.…”

Human gingival fibroblasts express functional chemokine receptor CXCR6

“…Moreover, they reported that the TLR-9 ligand suppressed IL-8 production from TLR-3 ligand-stimulated HGF [14]. Their report may explain why the TLR-9 ligand It is reported that both T helper type 1 (Th1) and Th2 cells exist in periodontally diseased tissues [15]. In this report, we reveal that the Th1-type cytokine, IFN-g, inhibited CXCR6 expression on HGF.…”