Direct Contact between T Lymphocytes and Human Dermal Fibroblasts or Synoviocytes Down-regulates Types I and III Collagen Production via Cell-associated Cytokines

Rezzonico, Roger; Burger, Danielle; Dayer, Jean‐Michel

doi:10.1074/jbc.273.30.18720

Cited by 74 publications

(50 citation statements)

References 49 publications

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“…[44][45][46] The next set of experiments was aimed at verifying whether long-lived neutrophils have the potential to interact with primary human fibroblasts. Neutrophils prelabeled with calcein-AM were incubated with confluent synovial fibroblasts and adherent neutrophils were observed by fluorescent microscopy.…”

Section: Adhesion To Primary Human Fibroblastsmentioning

confidence: 99%

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Chakravarti

Rusu

Flamand

et al. 2009

Laboratory Investigation

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Essential cells of innate immunity, neutrophils are often considered to be a homogenous population of terminally differentiated cells. During inflammation, neutrophils are extravasated cells exposed to local factors that prolong their survival and activate their production of mediators implicated in disease progression. In this study, a phenotypically distinct subset of human neutrophils that appear after prolonged exposure to cytokines was characterized. Freshly isolated neutrophils from healthy donors were incubated with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-a and interleukin (IL)-4, three cytokines that are locally present in various inflammatory conditions. Eight to 17% of neutrophils survived beyond 72 h. This subset of non-apoptotic neutrophils, as evaluated by three different markers, was enriched by discontinuous Percoll gradient centrifugation before studying their phenotype. These viable neutrophils showed neoexpression of HLA-DR, CD80 and CD49d. Compared with freshly isolated neutrophils, they responded differentially to second signals similar to formyl-methionyl-leucyl-phenylalanine with three-to four-fold increases in production of superoxide anions and leukotrienes. These cells augmented their phagocytic index by 141%, increased their adhesion to human primary fibroblasts, but reduced their migration in response to chemotactic stimuli and decreased exocytosis of primary and secondary granules. In addition, they produced substantial amounts of IL-8, IL-1Ra and IL-1b. This neutrophil subset had a unique profile of phosphorylation of intracellular signaling molecules. In conclusion, the present identification of a novel neutrophil phenotype highlights the reprogammable character of the neutrophil. This aspect is crucial for our understanding of its contribution to disease pathogenesis and host defense.

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Section: Adhesion To Primary Human Fibroblastsmentioning

confidence: 99%

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Chakravarti

Rusu

Flamand

et al. 2009

Laboratory Investigation

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“…Previous studies have also documented specific interactions between T cells and synovial fibroblasts that result in cell:cell adhesion (7)(8)(9). It has been shown that freshly activated T cells can trigger functionally relevant responses by synovial fibroblasts, in part mediated by the effects of membrane-bound cytokines such as TNF-␣ that can be produced by activated T cells (10,11). However, most T lymphocytes in RA synovium lack the morphology, surface phenotype, and cytokine secretion profile of T cell blasts (1).…”

mentioning

confidence: 99%

Effector Function of Resting T Cells: Activation of Synovial Fibroblasts

Yamamura

Gupta

Morita

et al. 2001

The Journal of Immunology

103

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Synovial tissue in rheumatoid arthritis is characterized by infiltration with large numbers of T lymphocytes and APCs as well as hyperplasia of synovial fibroblasts. Current understanding of the pathogenesis of RA includes the concept that synovial fibroblasts, which are essential to cartilage and bone destruction, are regulated by cytokines derived primarily from monocyte-macrophage cells. Recently it has been found that synovial fibroblasts can also function as accessory cells for T cell activation by superantigens and other stimuli. We have now found that highly purified resting T cells, even in the absence of T cell mitogens, induce activation of synovial fibroblasts when cocultured for 6–24 h. Such activation was evident by induction or augmentation of mRNA for stromelysin, IL-6, and IL-8, gene products important in joint inflammation and joint destruction. Furthermore, increased production of IL-6 and IL-8 was quantitated by intracellular cytokine staining and flow cytometry. This technique, previously used for analysis of T cell function, was readily adaptable for assays of synovial fibroblasts. Resting T cells also induced synovial fibroblasts to produce PGE2, indicating activation of expression of the cyclooxygenase 2 gene. Synergy was observed between the effects of IL-17, a cytokine derived from stimulated T cells that activates fibroblasts, and resting T lymphocytes. Various subsets of T cells, CD4+, CD8+, CD45RO+, and CD45RA+ all had comparable ability to induce synovial fibroblast activation. These results establish an Ag-independent effector function for resting T cells that is likely to be important in inflammatory compartments in which large numbers of T lymphocytes and fibroblasts can come into direct contact with each other.

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“…According to this perspective, Th2 cells may act by releasing profibrotic cytokines (IL-4, IL-13) (18)(19)(20) that induce fibroblasts to produce extracellular matrix components, and Th1 cells by releasing antifibrotic cytokines (interferon-␥ [IFN␥]) that inhibit extracellular matrix production (21). In addition, T lymphocytes may act directly on fibroblasts by cell-cell contact (21)(22)(23), and their effect may be mediated by other cells such as macrophages (24).…”

mentioning

confidence: 99%

Presence of CD4+CD8+ double‐positive T cells with very high interleukin‐4 production potential in lesional skin of patients with systemic sclerosis

Parel¹,

Aurrand-Lions²,

Scheja³

et al. 2007

Arthritis & Rheumatism

Self Cite

130

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Objective. Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin.Methods. We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo.Results. A distinct subset expressing both CD4 and CD8␣/␤ coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4؉ or CD8؉ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4؉ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo.Conclusion. The present findings show that T cells with the unusual CD4؉CD8؉ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts.

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Direct Contact between T Lymphocytes and Human Dermal Fibroblasts or Synoviocytes Down-regulates Types I and III Collagen Production via Cell-associated Cytokines

Cited by 74 publications

References 49 publications

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Effector Function of Resting T Cells: Activation of Synovial Fibroblasts

Presence of CD4+CD8+ double‐positive T cells with very high interleukin‐4 production potential in lesional skin of patients with systemic sclerosis

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