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Dive into the research topics where David Goldeck is active.

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Featured researches published by David Goldeck.


Current Opinion in Immunology | 2014

Inflammation, ageing and chronic disease

Graham Pawelec; David Goldeck; Evelyna Derhovanessian

Acute inflammatory responses are essential for pathogen control and tissue repair but can also cause severe collateral damage. Tight regulation of the response is required to minimize host injury, but in the face of chronic infections and age-associated immune dysregulation, inflammatory processes may exert multiple detrimental effects on the organism. The signs of low level systemic inflammation commonly detectable in elderly people are associated with many chronic diseases of ageing and may even contribute to their causation. The purpose of this article is to review recent literature from the past two years providing new data on the inter-relationships between inflammatory status and chronic diseases of ageing.


Journal of Alzheimer's Disease | 2009

Dramatic Shifts in Circulating CD4 but not CD8 T Cell Subsets in Mild Alzheimer's Disease

Anis Larbi; Graham Pawelec; Jacek M. Witkowski; Hyman M. Schipper; Evelyna Derhovanessian; David Goldeck; Tamas Fulop

The distribution of peripheral T cell subsets in young and healthy old people is markedly different, characterized by decreased numbers of naïve cells and increased numbers and clonal expansions of memory cells, predominantly in the CD8+ MHC class I-restricted subset. Here, however, we document dramatic alterations in naïve and memory subsets of CD4+ cells in patients with mild Alzheimers disease (AD), with greatly decreased percentages of naïve cells, elevated memory cells, and increased proportions of CD4+ but not CD8+ cells lacking the important costimulatory receptor CD28. CD4+CD25(high) potentially T regulatory cells with a naïve phenotype are also reduced in AD patients. Together these data provide stronger evidence than hitherto presented for more highly differentiated CD4+ as well as CD8+ T cells in AD patients, consistent with an adaptive immune system undergoing persistent antigenic challenge and possibly manifesting dysregulation as a result.


Journal of Neuroimmunology | 2012

Immune profiling of Alzheimer patients.

Mariavaleria Pellicanò; Anis Larbi; David Goldeck; Giuseppina Colonna-Romano; Silvio Buffa; Matteo Bulati; Graziella Rubino; Francesco Iemolo; Giuseppina Candore; Calogero Caruso; Evelyna Derhovanessian; Graham Pawelec

Alzheimers disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.


Journal of Leukocyte Biology | 2010

Induction of HIF-1α and the glycolytic pathway alters apoptotic and differentiation profiles of activated human T cells

Anis Larbi; Henning Zelba; David Goldeck; Graham Pawelec

The majority of in vitro studies involving lymphocytes is performed in AtmO2, and the PhysO2 that T cells encounter are variable but commonly much lower. Previous studies showed changed kinetics and delayed proliferation of human T cells at PhysO2. Here, we show that CD3/CD28‐dependent T cell activation induces faster cell cycling at AtmO2 than at PhysO2 (here taken to be 2%). Concomitantly with HIF‐1α expression, we observed a switch in the T cell respiratory pathway toward glycolysis at PhysO2. Thus, modulating available glucose levels showed that at PhysO2, T cells rely more on glycolysis, associated with a higher phosphorylation of Aktser473. Although no difference in spontaneous apoptosis of resting cells was detected, it was increased significantly at PhysO2 after T cell activation and was different within the different T cell subsets. This may explain at least partly the differently altered proliferation and subset distribution observed in CD4+ and CD8+ T cells as a result of differences in naïve and memory subset distribution. Together, these findings suggest that T cell activation thresholds, subsequent proliferative capacity, and susceptibility to apoptosis, hitherto studied in air and thought to be crucial for monitoring immune responsiveness, may require re‐assessment.


Age | 2013

A novel B cell population revealed by a CD38/CD24 gating strategy: CD38−CD24− B cells in centenarian offspring and elderly people

Silvio Buffa; Mariavaleria Pellicanò; Matteo Bulati; Adriana Martorana; David Goldeck; Calogero Caruso; Graham Pawelec; Giuseppina Colonna-Romano

The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19+CD38−CD24−, which we find at higher frequencies in the elderly but less so in CO than healthy age-matched random controls. In addition, we found a decreased expression of RP105 (CD180), a toll-like receptor-associated molecule, on these cells. CD180 downregulation may potentially be a marker of immunosenescence. Moreover, we show that these CD19+CD38−CD24− B cells produce TNF and hypothesize that their observed expansion in the elderly might contribute to the increased inflammatory status sometimes designated “inflamm-aging.”


Age | 2013

Aging affects the proportions of T and B cells in a group of elderly men in a developing country-a pilot study from Pakistan

Iftikhar Alam; David Goldeck; Anis Larbi; Graham Pawelec

Immune status is different in the elderly and the young, but whether age-associated differences are similar in developing and industrialized countries is unclear. To approach this question, peripheral blood immune cell phenotypes were analyzed by polychromatic flow cytometry in 50 young and 50 elderly men in a pilot study in a rural area of Pakistan. As a group, the elderly had a significantly lower CD4:CD8 ratio, a lower percentage of CD8+ naïve T cells, and significantly higher percentage of late-differentiated memory cells than the young. No age-associated differences were seen in B cells or NK cells. CD8+ cells as a percentage of CD3+ T cells were positively associated with plasma CRP levels but not other factors. We conclude that there are differences between the peripheral immune cell phenotypes of young and elderly Pakistani men and that these seem broadly similar to those more extensively documented in industrialized countries, despite the marked societal, nutritional, and many other differences in these populations.


Current Alzheimer Research | 2016

Peripheral Immune Signatures in Alzheimer Disease

David Goldeck; Jacek M. Witkowski; Tamas Fulop; Graham Pawelec

According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in the brain. It further promotes the hyperphosphorylation of the tau protein which forms characteristic neurofibrillary tangles and thereby loses its important role in axonal transport and contributes to neurodegeneration. Therefore, treatments have targeted Aβ, but clinical trials of immunotherapies caused severe side effects and showed that Aβ clearance alone did not result in any cognitive improvement. This leads to the question: what else promotes AD pathology? Here, we review data on systemic inflammation and the possible roles that the immune system might play in AD. Microglia and astrocytes are activated and secrete inflammatory cytokines and chemokines. Via a disturbed blood-brain barrier, peripheral immune cells are activated and recruited towards inflamed brain lesions and amyloid plaques, but due to the chronic nature of the amyloid burden and their reduced function, these cells are not able to control inflammation and the associated detrimental immune responses. In addition, age-related inflammation and chronic infection with herpes viruses might contribute to the systemic inflammation and exacerbate attempts to restore the balance of inflammation.


PLOS ONE | 2013

Enhanced Chemokine Receptor Expression on Leukocytes of Patients with Alzheimer's Disease

David Goldeck; Anis Larbi; Mariavaleria Pellicanò; Iftikhar Alam; Inga Zerr; Christian Schmidt; Tamas Fulop; Graham Pawelec

Although primarily a neurological complaint, systemic inflammation is present in Alzheimers Disease, with higher than normal levels of proinflammatory cytokines and chemokines in the periphery as well as the brain. A gradient of these factors may enhance recruitment of activated immune cells into the brain via chemotaxis. Here, we investigated the phenotypes of circulating immune cells in AD patients with multi-colour flow cytometry to determine whether their expression of chemokine receptors is consistent with this hypothesis. In this study, we confirmed our previously reported data on the shift of early- to late-differentiated CD4+ T-cells in AD patients. The percentage of cells expressing CD25, a marker of acute T-cell activation, was higher in patients than in age-matched controls, and percentages of CCR6+ cells were elevated. This chemokine receptor is primarily expressed on pro-inflammatory memory cells and Th17 cells. The proportion of cells expressing CCR4 (expressed on Th2 cells) and CCR5 (Th1 cells and dendritic cells) was also greater in patients, and was more pronounced on CD4+ than CD8+ T-cells. These findings allow a more detailed insight into the systemic immune status of patients with Alzheimers disease and suggest possible novel targets for immune therapy.


Journal of Immunoassay & Immunochemistry | 2012

FLOW CYTOMETRIC LYMPHOCYTE SUBSET ANALYSIS USING MATERIAL FROM FROZEN WHOLE BLOOD

Iftikhar Alam; David Goldeck; Anis Larbi; Graham Pawelec

Multicenter immune monitoring programs commonly rely on storing and shipping cryopreserved peripheral blood mononuclear cells (PBMC), isolated from whole blood before freezing. However, under many conditions in the field, facilities to separate PBMC are absent. Here, we investigate the feasibility of using whole blood (WB) frozen at −80°C as a source of viable lymphocytes for use in immunological studies. We compare the percentage of CD4 and CD8 T lymphocytes and their subsets from frozen WB with results from cryopreserved PBMC in five random healthy blood donors (three female, two male). We report that CD4 and CD8 values in lymphocytes from WB frozen up to 120 days were very similar to those of PBMC frozen up to 10 days. These data suggest that within the limits of parameters investigated in this study, contrary to our original assumptions, whole blood frozen at −80°C may in fact be an appropriate source of viable lymphocytes for T cell enumeration assays in immunological and epidemiological studies.


Stem Cell Research & Therapy | 2016

Bone marrow-derived mesenchymal stromal cells differ in their attachment to fibronectin-derived peptides from term placenta-derived mesenchymal stromal cells

Jan K. Maerz; Lorenzo Pietro Roncoroni; David Goldeck; Tanja Abruzzese; Hubert Kalbacher; Bernd Rolauffs; Peter DeZwart; Kay Nieselt; Melanie L. Hart; Gerd Klein; Wilhelm K. Aicher

IntroductionHuman mesenchymal stromal cells (MSCs) can be isolated from different sources including bone marrow and term placenta. These two populations display distinct patterns of proliferation and differentiation in vitro. Since proliferation and differentiation of cells are modulated by cell–matrix interactions, we investigated the attachment of MSCs to a set of peptide-coated surfaces and explored their interactions with peptides in suspension.MethodsHuman MSCs were isolated from bone marrow and term placenta and expanded. Binding of MSCs to peptides was investigated by a cell-attachment spot assay, by blocking experiments and flow cytometry. The integrin expression pattern was explored by a transcript array and corroborated by quantitative reverse transcription polymerase chain reaction and flow cytometry.ResultsExpanded placenta-derived MSCs (pMSCs) attached well to surfaces coated with fibronectin-derived peptides P7, P15, and P17, whereas bone marrow-derived MSCs (bmMSCs) attached to P7, but barely to P15 and P17. The binding of bmMSCs and pMSCs to the peptides was mediated by β1 integrins. In suspension, expanded bmMSCs barely bind to P7, P13, P15, and less to P14 and P17. Ex vivo, bmMSCs failed to bind P7, but displayed a weak interaction with P13, P14, and P15. In suspension, expanded pMSCs displayed binding to many peptides, including P4, P7, P13, P14, P15, and P17. The differences observed in binding of bmMSCs and pMSCs to the peptides were associated with significant differences in expression of integrin α2-, α4-, and α6-chains.ConclusionsHuman bmMSCs and pMSCs show distinct patterns of attachment to defined peptides and maintain differences in expression of integrins in vitro. Interactions of ex vivo bmMSCs with a given peptide yield different staining patterns compared to expanded bmMSCs in suspension. Attachment of expanded MSCs to peptides on surfaces is different from interactions of expanded MSCs with peptides in suspension. Studies designed to investigate the interactions of human MSCs with peptide-augmented scaffolds or peptides in suspension must therefore regard these differences in cell–peptide interactions.

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Graham Pawelec

Université de Sherbrooke

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Tamas Fulop

University of Tübingen

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