Programmed cell death and extrathymic reduction of Vβ8+CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B

Kawabe, Yojiro; Ochi, Atsuo

doi:10.1038/349245a0

Cited by 638 publications

(376 citation statements)

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“…administration of superantigen causes activation of T cells with the corresponding Vb chain, followed by deletion of these cells both in neonatal [12] and in adult mice [24][25][26][27]. However, the T-cell levels are restored to normal within a few weeks [28].…”

Section: Discussionmentioning

confidence: 99%

“…The number of eosinophils in BALF and levels of total and OVA-specific IgE are shown in Fig. 5A-C.Lymphocytes isolated from SEA and sham-treated mice are similar in proportion and activation pattern Systemic superantigen treatment is known to lead to expansion of T cells followed by deletion of cells with the affected Vb receptors [12,[24][25][26][27]. In order to investigate whether neonatally SEA primed mice differed from sham-treated mice with respect to lymphocyte or APC availability by the time point for oral tolerisation, we isolated cells from the MLN and spleen at 6 wk of age and analysed them by flow cytometry for the presence of memory, naïve and activated T cells (CD4 1 , CD8 1 and Treg cells), B cells and DC.…”

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confidence: 97%

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Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

et al. 2009

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The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T-cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre-treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung-cell infiltration and antigen-specific IgE response in the SEA pre-treated mice, compared with sham-treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre-treated mice that were fed with PBS showed similar inflammatory response as the sham-treated PBS-fed mice. Our results suggest that strong T-cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance.Key words: Allergic sensitisation . Mucosal immunity . Staphylococcal enterotoxin A . Tolerance Supporting Information available online IntroductionAllergies have increased markedly in Western industrialised countries, where they now afflict every third child. Allergies are linked to wealth, good education and small families, observations that have given rise to the hygiene hypothesis, according to which the developing immune system should be exposed to appropriate microbial stimulation in early childhood in order to mature correctly and for allergies to be avoided [1,2]. The hygiene hypothesis is also supported by experimental data. Germ-free animals are less prone to develop oral Ã These author contributed equally to this work. Eur. J. Immunol. 2009. 39: 447-456 DOI 10.1002 Immunomodulation 447 tolerance than animals reared conventionally [3,4]. Oral tolerance is induced by passage of antigens over the gut mucosa, prevents against both Th1-and Th2-dominated immune responses [5] and includes development of Treg [6,7]. Natural thymic-dependent Treg (CD4 1 CD25 hi FoxP3 1 ) are fundamental in protection against autoimmunity, gut inflammation and IgE responses. This cell subset has reduced functional capacity in germ-free animals [8].The strongest T-cell activators known are the ''superantigens'', exotoxins produced by certain pathogenic bacteria such as Staphylococcus aureus. These include staphylococcal enterotoxin A, B, C, D and E, as well as toxic shock syndrome toxin-1. The superantigen binds to the variable part of the TCR and to the MHC class II molecule, thereby ''mimicking'' antigen recognition, which leads to T-cell activation [9][10][11][12]. As many as 10-30% of all T cells can become activated by a certain superantigen compared with o0...

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Section: Discussionmentioning

confidence: 99%

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confidence: 97%

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

et al. 2009

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“…This phenomenon was termed antagonistic pleiotropy. Deletion of antigenspecific T cells in the periphery was demonstrated to occur via apoptosis in 1991 [54]. Arguably, 1995 was the year of CD95, when three independent research groups published the finding that the CD95/CD95L system is the major inducer of AICD at least in vitro [55][56][57].…”

Section: Apoptosis In the Immune System Central Tolerance -Education mentioning

confidence: 99%

How apoptosis got the immune system in shape

Feig

Marynen

2007

Eur. J. Immunol.

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“…Induction of apoptosis is a key mechanism to delete autoreactive T cells during thymic selection [9] and to eliminate activated T cells in the periphery during the termination of an immune response [10]. CD95, also known as APO-1 or Fas, is a member of the death receptor family [11] important for T cell homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs

Strauß

Osen

Debatin

2002

Clinical and Experimental Immunology

150

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SUMMARYImmunosuppressive drugs (ISD) are used for the prevention and treatment of graft rejection, graftversus-host-disease (GVHD) and autoimmune disorders. The precise mechanisms by which ISD interfere with T cell activation and effector function or delete antigen-specific T cells are defined only partially. We analysed commonly used ISD such as dexamethasone (DEX), mycophenolic acid (MPA), FK506, cyclosporin A (CsA), rapamycin (RAP), methotrexate (MTX) and cyclophosphamide (CP) for apoptosis-induction and modulation of activation and effector function in human peripheral T cells, cytotoxic T cell lines (CTL) and Jurkat T cells. Of all drugs tested only CP and MTX prevented antigenspecific proliferation of T cells and decreased cytotoxicity of alloantigen specific CTL lines by direct induction of apoptosis. MTX and CP also slightly increased activation-induced cell death (AICD) and CD95-sensitivity. In contrast, all other drugs tested did not induce T cell apoptosis, increase CD95-sensitivity or AICD. CsA and FK506 even prevented AICD by down-modulation of CD95L. DEX, MPA, CsA, FK506 and RAP inhibited activation of naive T cells, but were not able to block proliferation of activated T cells nor decrease cytotoxic capacity of CTL lines. These results show that ISD can be classified according to their action on apoptosis-induction and inhibition of proliferation and would favour a rational combination therapy to delete existing reactive T cells and prevent further T cell activation.

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Programmed cell death and extrathymic reduction of Vβ8+CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B

Cited by 638 publications

References 26 publications

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

How apoptosis got the immune system in shape

Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs

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