Interplay between superantigens and the immune system

Irwin, M. J.; Gascoigne, Nicholas R. J.

doi:10.1002/jlb.54.5.495

Cited by 33 publications

(25 citation statements)

References 109 publications

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“…Another characteristic of superantigens is that they can activate both CD4+ and CD8+ T cell subsets and, as a consequence of the massive activation and proliferation of T cells, they are responsible for the production of large amounts of proinflammatory cytokines. 26 Hypothetical superantigen stimulation may explain most of the results of the present study (fig 4). It can be postulated that patients with PMR and GCA have encountered a viral or bacterial superantigen specific for a particular BV(s) element(s).…”

Section: Discussionsupporting

confidence: 54%

“…Dramatic T cell expansions occur more frequently with superantigens. 26 Superantigens have been implicated in the pathogenesis of other vasculitic syndromes, such as Kawasaki's disease, and other autoimmune disorders, such as rheumatoid arthritis, myasthenia gravis, or Crohn's disease. [38][39][40][41] Superantigens interact with the immune system by binding in an unrestricted way to the MHC class II proteins and activating T cells through the TCR BV region.…”

Section: Discussionmentioning

confidence: 99%

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Selective T cell receptor decrease in peripheral blood T lymphocytes of patients with polymyalgia rheumatica and giant cell arteritis

López‐Hoyos

2004

Annals of the Rheumatic Diseases

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Objectives: To investigate the phenotype and T cell receptor (TCR) use in peripheral blood T cells in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Methods: Circulating T lymphocyte phenotype and TCR repertoire were studied by flow cytometry using specific monoclonal antibodies in 23 healthy controls and 37 patients with PMR/GCA. Results: Patients with active PMR/GCA showed an inverse relation between naive and memory CD4+ T cells and unchanged expression of activation surface markers compared with controls. CD4+ TCR BV expansions were seen in 12 (52%) controls and in 8 (22%) patients with active disease (p = 0.03). Within the CD8+ subset, the frequency of expansions was similar between groups. Most T cell expansions remained stable over time. Seventeen of the 23 patients with active PMR/GCA disclosed a simultaneous CD4+ and CD8+ T cell depletion for at least one particular BV family with a clear predominance of BV5S2/S3. Conclusions: The phenotype of circulating T cells in patients with PMR/GCA is similar to that found in aged healthy subjects, except for the surface markers of naive and memory cells and a striking non-activated phenotype. Specific BV expansions in CD4+ and CD8+ T cells, which remain stable over time, are frequent in aged subjects, including patients with PMR/GCA. TCR BV changes in patients with active disease seem to be also age related, except for the significant decrease in certain BV families in both CD4+ and CD8+ T cell subsets, which may favour the participation of a superantigen stimulation in PMR/GCA. G iant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely related syndromes affecting elderly people.1 GCA is a granulomatous vasculitis affecting medium and large sized arteries, and the inflammatory lesions are characterised by the presence of mononuclear cells, multinuclear giant cells, and fragmentation of the internal elastic laminae.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Selective T cell receptor decrease in peripheral blood T lymphocytes of patients with polymyalgia rheumatica and giant cell arteritis

López‐Hoyos

2004

Annals of the Rheumatic Diseases

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“…In CD, SEE failed to stimulate the cytotoxic function of Vj^S T cells, in spite ofthe fact thai SEE expanded this T cell subset. Staphylococcal enterotoxins have been shown to alTect human T cell function [15,29] and modulate the responsiveness T cell clones to antigen without altering their proliferaiive capacity lo IL-2 [30]. On the other hand.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

Baca-Estrada

Wong

Croitoru

1995

Clinical and Experimental Immunology

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SUMMARYIn Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A)-stimuiated peripheral blood mononuclear celts (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of \3^ T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8 ^ T cells expressing V/38. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of V/?8 and V/312 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the V/312 subset, SEE stimulation failed to increase cytolytic activity of V/38^ T cells in spile of the expansion of V/38^ Tceils. These results suggest that the changes in cytotoxic function observed in V/38 T cells in Crohn's patients may reflect previous exposure to a V/58-seIective superantigen.

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“…SEB is an S. aureus-derived enterotoxin, which belongs to a family of related proteins defined as superantigens due to their capacity to induce intensive Tcell activation and proliferation independent of classical antigen processing by macrophages and dendritic cells (20). Superantigens bind to major histocompatibility complex-encoded class II proteins outside the normal antigen-presenting groove and to variable regions of T-cell receptor ␤ chains (20), causing massive release of proinflammatory mediators and, ultimately, tissue injury (15). In order to study SEB-induced leukocyte recruitment, we utilized the murine subcutaneous air pouch model, which has been shown to be a suitable in vivo approach for defining the mechanisms and kinetics of inflammatory leukocyte recruitment, allowing not only quantification of leukocyte subtypes but also analyses of secreted substances, such as chemokines (23,26,31,36).…”

Section: Fig 4 Time-dependent Leukocyte Response To Seb Animals Rementioning

confidence: 99%

Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

Schramm

Thorlacius

2003

Infect Immun

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This study was conducted to examine the anti-inflammatory mechanisms of dexamethasone during leukocyte recruitment and expression of the CXC chemokines macrophage inflammatory protein 2 (MIP-2) (CXCL2) and cytokine-induced neutrophil chemoattractant (KC) (CXCL1) in staphylococcal enterotoxin B (SEB)-induced acute inflammation. To do this, SEB was injected into murine air pouches with or without dexamethasone pretreatment for 2 h. SEB induced infiltration of leukocytes in a dose-and time-dependent manner, with the maximal response observed after 4 h of treatment with 10 g of SEB. The recruited leukocytes comprised more than 77% neutrophils. Moreover, SEB challenge (10 g) provoked time-dependent secretion of CXC chemokines, which peaked after 1 h. Local administration of antibodies against MIP-2 and KC significantly reduced SEB-triggered neutrophil accumulation by 38 and 59%, respectively. Dexamethasone (10 mg kg ؊1 ) significantly decreased neutrophil recruitment by 82% and reduced secretion of MIP-2 and KC by 89 and 85%, respectively, in response to SEB challenge. Our data demonstrate that dexamethasone potently inhibits neutrophil recruitment in SEB-induced inflammation. Moreover, we provide evidence that MIP-2 and KC are key mediators in the neutrophil response to SEB. Furthermore, our findings demonstrate that dexamethasone attenuates SEB-induced expression of MIP-2 and KC. Thus, this study elucidates important signaling pathways of SEB-induced neutrophil recruitment and anti-inflammatory mechanisms of action of dexamethasone.

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Interplay between superantigens and the immune system

Cited by 33 publications

References 109 publications

Selective T cell receptor decrease in peripheral blood T lymphocytes of patients with polymyalgia rheumatica and giant cell arteritis

Selective T cell receptor decrease in peripheral blood T lymphocytes of patients with polymyalgia rheumatica and giant cell arteritis

Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

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