Activation and clonal expansion of human Myelin Basic Protein-reactive T cells by bacterial superantigens

Zhang, Jingwu; Vandevyver, Caroline; Stinissen, Piet; Mertens, Nadja; Berg-Loonen, E. van den; Raus, Jef

doi:10.1016/0896-8411(95)90012-8

Cited by 26 publications

(20 citation statements)

References 32 publications

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“…Indeed, infectious agents were frequently linked to disease development and clinical exacerbation in MS [9]. For example, viral or bacterial superantigens can lead to activation of myelin reactive T cells in a TCR bV chain specific manner [10]. Autoreactive T cells may also become activated through recognition of microbial epitopes that share sequence homology with autoantigens.…”

Section: Activation Of Myelin Reactive T Cells In Msmentioning

confidence: 99%

Activation of myelin reactive T cells in multiple sclerosis: A possible role for T cell degeneracy?

Stinissen

Hellings

2008

Eur J Immunol

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While it is widely accepted that myelin reactive T cells are key players in the immunopathogenesis of multiple sclerosis (MS), the initial triggers that turn on these self-reactive T-cells remain to be determined. One mechanism, which is already text book knowledge for a decade, is molecular mimicry by which viral or microbial antigens are able to cross-activate T cells specific for myelin epitopes, the major target in MS pathology. Although proof of concept for this principle was given in animal model studies, evidence for such a mechanism in MS is limited. In this issue, Zhang et al. demonstrate an increased frequency of T cells that cross-react with a wide variety of antigens, a phenomenon termed as T cell degeneracy. While the role of these degenerate T cells in MS remains to be determined the authors now provide new elegant tools to study this T cell population, thus providing a starting point to better understand their function in MS.

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Section: Activation Of Myelin Reactive T Cells In Msmentioning

confidence: 99%

Activation of myelin reactive T cells in multiple sclerosis: A possible role for T cell degeneracy?

Stinissen

Hellings

2008

Eur J Immunol

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“…On the other hand, several lines of evidence show that staphylococcal superantigens SEA, SEB and SEC are involved in the exacerbation of atopic dermatitis (AD) [4, 5, 6]. It is well known that AD patients show a striking susceptibility to infection and colonization of Staphylococcus aureus.…”

Section: Introductionmentioning

confidence: 99%

“…In a mouse MS model, experimental autoimmune encephalomyelitis and staphylococcal enterotoxins A and B (SEA and SEB, respectively) reactivated CNS inflammation [2, 3]and induced epitope spreading [4]. In humans, Zhang et al [5]and Hermans et al [6]showed that bacterial superantigens (SEA and SEB) could stimulate myelin basic protein (MBP)-reactive T cell clones from MS patients, resulting in the production of proinflammatory cytokines such as IFN-γ. Although a similar reaction has also been observed in MBP-reactive T cell clones from healthy controls [5], differences in the cytokine profile of MBP-reactive T cells have been shown in MS patients and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

“…In humans, Zhang et al [5]and Hermans et al [6]showed that bacterial superantigens (SEA and SEB) could stimulate myelin basic protein (MBP)-reactive T cell clones from MS patients, resulting in the production of proinflammatory cytokines such as IFN-γ. Although a similar reaction has also been observed in MBP-reactive T cell clones from healthy controls [5], differences in the cytokine profile of MBP-reactive T cells have been shown in MS patients and healthy controls. That is, an increased production of IL-2, IL-4, TNF-α, IFN-γ and IL-10 was seen in MS patients, while in MS patients carrying the HLA-DRB1*1501 allele, an especially large increase in TNF-α was seen [6].…”

Section: Introductionmentioning

confidence: 99%

“…These observations suggest that allergic mechanisms might be partly involved in atopic myelitis. On the other hand, the TCR Vβ types stimulated by staphylococcal superantigens and carried on the T cells infiltrating into the S. aureus -colonized skin in AD patients [18, 19]are in part common to those of the MBP-reactive T cells activated by bacterial superantigens in MS patients and healthy controls (Vβ12 or Vβ17) [5, 6]. Therefore, in patients with atopic myelitis, autoimmune mechanisms might also be involved in which staphylococcal superantigens activate T cells bearing the homing receptor to skin, cutaneous lymphocyte antigen, on the one hand, and those reactive to MBP on the other through stimulation of TCR Vβ12 or Vβ17.…”

Section: Introductionmentioning

confidence: 99%

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Presence of IgE Antibodies to Bacterial Superantigens and Increased IL-13-Producing T Cells in Myelitic Patients with Atopic Diathesis

Ochi

Osoegawa

Murai

et al. 2004

Int Arch Allergy Immunol

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Background: Superantigens are considered to exacerbate autoimmune inflammation through the expansion of autoreactive T cells; however, the immune response to bacterial superantigens has not been extensively studied in any type of myelitis. We recently reported the occurrence of a distinct type of myelitis in patients with atopic diathesis, which in a recent nationwide survey was reported to be widespread in Japan. The aim of this study was to investigate the presence of IgE antibodies to bacterial superantigens and the proportion of IL-13- or IL-5-producing CD4+ or CD8+ T cells in patients with myelitis and atopic diathesis. Methods: Twenty-four myelitic patients with and 12 myelitic patients without hyperIgEemia, 28 patients with multiple sclerosis (MS) and 34 healthy controls were enrolled in this study. IgE antibodies to staphylococcal enterotoxins A (SEA) and B (SEB) in sera were measured using a liquid-phase enzyme immunoassay, and the intracellular production of IL-5 and IL-13 in peripheral blood CD4+ and CD8+ T cells was measured by flow cytometry. Results: The myelitic patients with hyperIgEemia showed significantly higher positive rates of serum SEA/SEB-specific IgE antibodies (41.7 and 62.5%, respectively) than the healthy controls (5.9 and 8.8%), patients with MS (0 and 21.4%) and those with normoIgEemic myelitis (0 and 0%). Moreover, IL-13-producing CD4+ T cells and CD8+ T cells increased significantly in the myelitic patients with hyperIgEemia compared to the controls, while IL-5-producing CD4+ or CD8+ T cells did not. Conclusions: The IgE response to staphylococcal superantigens is heightened in myelitic patients with atopic diathesis, which might contribute to increases in IL-13-producing T cells and thus the development of myelitis.

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Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data

Stinissen¹,

Zhang²,

Medaer³

et al. 1996

J. Neurosci. Res.

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Activation and clonal expansion of human Myelin Basic Protein-reactive T cells by bacterial superantigens

Cited by 26 publications

References 32 publications

Activation of myelin reactive T cells in multiple sclerosis: A possible role for T cell degeneracy?

Activation of myelin reactive T cells in multiple sclerosis: A possible role for T cell degeneracy?

Presence of IgE Antibodies to Bacterial Superantigens and Increased IL-13-Producing T Cells in Myelitic Patients with Atopic Diathesis

Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data

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