Regulatory T cells control the transition from acute into chronic inflammation in glucose-6-phosphate isomerase-induced arthritis

Frey, Oliver; Reichel, Andreas; Bonhagen, Kerstin; Morawietz, Lars; Rauchhaus, Una; Kamradt, Thomas

doi:10.1136/ard.2009.123422

Cited by 42 publications

(49 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The goal of our work was to examine, in well-described glucose-6-phosphate isomerase (G6PI)-induced murine arthritis [11-17], whether 18 F-FDG micro-PET/CT can be used for the quantitative in vivo assessment of inflammation in acute and chronic stages of experimental arthritis. To validate the method, results were systematically compared with semiquantitative histopathological analyses.…”

Section: Introductionmentioning

confidence: 99%

In vivo molecular imaging of experimental joint inflammation by combined 18F-FDG positron emission tomography and computed tomography

et al. 2010

View full text Add to dashboard Cite

IntroductionThe purpose of this work was to establish and validate combined small animal positron emission tomography - computed tomography (PET/CT) as a new in vivo imaging method for visualisation and quantification of joint inflammation.MethodsSignalling of radioisotope 18F labelled Fluorodeoxyglucose (18F-FDG) injected in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis was analysed by PET/CT. Accumulation of 18F-FDG in tissue was quantified by PET measurement, whereas high definition CT delivered anatomical information. The fusion of both images revealed in detail spatial and temporal distribution and metabolism of 18F-FDG.ResultsA distinct 18F-FDG signal could be measured by PET in carpal and tarsal joints, from mice with early or established arthritis. In contrast, no accumulation of 18F-FDG was detectable before arthritis onset. Comparison of 18F-FDG joint uptake with histopathological evaluation revealed a significant correlation of both methods.ConclusionsSmall animal PET/CT using 18F-FDG is a feasible method for monitoring and, more importantly, quantitative assessment of inflammation in G6PI-arthritis. Since it is possible to perform repeated non-invasive measurements in vivo, not only numbers of animals in preclinical studies can markedly be reduced by this method, but also longitudinal studies come into reach, e. g. for individual flare-up reactions or monitoring therapy response in progressive arthritis.

show abstract

Section: Introductionmentioning

confidence: 99%

In vivo molecular imaging of experimental joint inflammation by combined 18F-FDG positron emission tomography and computed tomography

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Interestingly, the strong dependency of the expression of one cytokine on the expression of others which we found reproducibly between different time points and despite differing genotypes implies some biological significance of these findings. We have previously shown in a kinetic study that TNF-α is one of the earliest cytokines produced after activation of antigen-specific T cells (Frey et al, 2010b). Given that expression of the other cytokines starts later, the strong relationship between TNF-α and the expression of the other cytokines could argue for a hard-wired connection between the expression of these mediators.…”

Section: Discussionmentioning

confidence: 99%

“…The cells were stained and analyzed for the expression of six cytokines as described in the following. DBA/1 mice in the age of 6–12 weeks were subcutaneously immunized at the base of the tail with recombinant glucose-6-phosphate isomerase (G6PI) in an emulsion containing also Freunds complete adjuvant as described (Bruns et al, 2009; Frey et al, 2010a,b, 2011a,b). At day 21 after immunization, the draining lymph nodes (inguinal, axillary, paraaortic) were aseptically removed and prepared to a single cell suspension.…”

Section: Methodsmentioning

confidence: 99%

“…The aim of our study was to test the feasibility of this approach for the identification of structural patterns in flow cytometric data. We used data sets from experiments where the expression of six cytokines in antigen-specific T helper (Th) cells from a murine arthritis model were analyzed (Schubert et al, 2004; Frey et al, 2010b). Our results show that the supervised machine learning method induction of decision trees is a versatile tool for identification of structural patterns in multidimensional data obtained by flow cytometry.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multivariate Analysis of Flow Cytometric Data Using Decision Trees

Simon¹,

Guthke²,

Kamradt³

et al. 2012

Front. Microbio.

View full text Add to dashboard Cite

Characterization of the response of the host immune system is important in understanding the bidirectional interactions between the host and microbial pathogens. For research on the host site, flow cytometry has become one of the major tools in immunology. Advances in technology and reagents allow now the simultaneous assessment of multiple markers on a single cell level generating multidimensional data sets that require multivariate statistical analysis. We explored the explanatory power of the supervised machine learning method called “induction of decision trees” in flow cytometric data. In order to examine whether the production of a certain cytokine is depended on other cytokines, datasets from intracellular staining for six cytokines with complex patterns of co-expression were analyzed by induction of decision trees. After weighting the data according to their class probabilities, we created a total of 13,392 different decision trees for each given cytokine with different parameter settings. For a more realistic estimation of the decision trees’ quality, we used stratified fivefold cross validation and chose the “best” tree according to a combination of different quality criteria. While some of the decision trees reflected previously known co-expression patterns, we found that the expression of some cytokines was not only dependent on the co-expression of others per se, but was also dependent on the intensity of expression. Thus, for the first time we successfully used induction of decision trees for the analysis of high dimensional flow cytometric data and demonstrated the feasibility of this method to reveal structural patterns in such data sets.

show abstract

“…Furthermore, fine phenotypic analysis of TCR-TgB mice revealed a lower percentage of ICOS high CD4 + T cells, probably follicular T helper cells (Tfh), which are critical in systemic autoimmunity by supporting autoreactive B cells [117]. ICOS has been shown to be indispensable in collagen-induced and K/BxN arthritis models [118–120], and certain ICOS polymorphisms are associated with RA [121]. The importance of costimulatory signals in RA (Figure 3(a)) is also supported by the successful clinical use of Abatacept, a recombinant fusion protein of CTLA-4 [122].…”

Section: T Cell Receptor (Tcr) Signaling and Apoptosis In Arthritismentioning

confidence: 99%

Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

Hanyecz

Olasz

Tarjányi

et al. 2014

BioMed Research International

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.

show abstract

Regulatory T cells control the transition from acute into chronic inflammation in glucose-6-phosphate isomerase-induced arthritis

Cited by 42 publications

References 38 publications

In vivo molecular imaging of experimental joint inflammation by combined 18F-FDG positron emission tomography and computed tomography

In vivo molecular imaging of experimental joint inflammation by combined 18F-FDG positron emission tomography and computed tomography

Multivariate Analysis of Flow Cytometric Data Using Decision Trees

Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

Contact Info

Product

Resources

About