Staphylococcal enterotoxin B induces anergy to conventional peptide in memory T cells

Watson, Andrew R.O.; Mittler, James N.; Lee, William T.

doi:10.1016/s0008-8749(03)00117-5

Cited by 19 publications

(33 citation statements)

References 42 publications

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“…These cells arise due to original stimulation through a dual-expressed TCR composed of the transgenic TCR V␤-chain paired with an endogenous TCR V␣-chain (29). As previously discussed, these cells are typical memory CD4 cells (34). In the current study, we evaluated immunological synapses formed during naive vs memory cell cognate interactions with APCs.…”

Section: Conjugation Of Apcs With Naive or Memory Cd4 T Cellsmentioning

confidence: 87%

“…Surprisingly, we report that all of the memory cell TCRs were found in the synapse. Because DO11.10 memory cells coexpress alternate TCRs to varying degrees (29,33,34), this suggests that both occupied and nonengaged (non-OVAspecific) TCRs migrate to the synapse. This may be related to their constitutive association with lipid rafts.…”

Section: Discussionmentioning

confidence: 99%

“…The transgenic TCR is specifically recognized by the anti-clonotype mAb, KJ1-26 (24). We have previously reported on the generation and characterization of memory cells that bear the clonotypic TCR in DO11.10 mice (29,33,34). Of note, KJ1-26 ϩ , OVA-specific memory T cells were obtained from unmanipulated mice.…”

Section: Conjugation Of Apcs With Naive or Memory Cd4 T Cellsmentioning

confidence: 99%

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Differences in Signaling Molecule Organization between Naive and Memory CD4+ T Lymphocytes

Watson

Lee

2004

The Journal of Immunology

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The immunological synapse is a highly organized complex formed at the junction between Ag-specific T cells and APCs as a prelude to cell activation. Although its exact role in modulating T cell signaling is unknown, it is commonly believed that the immunological synapse is the site of cross-talk between the T cell and APC (or target). We have examined the synapses formed by naive and memory CD4 cells during Ag-specific cognate interactions with APCs. We show that the mature immunological synapse forms more quickly during memory T cell activation. We further show that the composition of the synapse found in naive or memory cell conjugates with APCs is distinct with the tyrosine phosphatase, CD45, being a more integral component of the mature synapses formed by memory cells. Finally, we show that signaling molecules, including CD45, are preassociated in discrete, lipid-raft microdomains in resting memory cells but not in naive cells. Thus, enhanced memory cell responses may be due to intrinsic properties of signaling molecule organization.

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Section: Conjugation Of Apcs With Naive or Memory Cd4 T Cellsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Conjugation Of Apcs With Naive or Memory Cd4 T Cellsmentioning

confidence: 99%

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Differences in Signaling Molecule Organization between Naive and Memory CD4+ T Lymphocytes

Watson

Lee

2004

The Journal of Immunology

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“…This tolerance may be induced by T cell anergy and a shift towards a Th2-type response (Miller et al, 1999;Watson et al, 2003). The mechanism for this is not fully understood, although regulatory cytokines may play a role.…”

Section: Introductionmentioning

confidence: 99%

Relationship of varying patterns of cytokine production to the anorexic and neuroendocrine effects of repeated Staphylococcal enterotoxin A exposure☆

Urbach-Ross

Crowell

Kusnecov

2008

Journal of Neuroimmunology

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Staphylococcal enterotoxin A (SEA) is a superantigen that stimulates T cells and induces the production of multiple cytokines. Previous studies have shown that SEA augments gustatory neophobia and activates the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to determine if the cytokine response, behavioral effects, and HPA axis activation persisted after repeated SEA treatment. Male C57BL/6J mice were given 1-4 intraperitoneal injections of 5 μg SEA, after which food intake, corticosterone, or peripheral cytokines were measured. In a series of experiments, it was found that secondary exposure to SEA two or three days after priming increased corticosterone, but attenuated splenic TNFα, while augmenting IL-1β, IL-2, and IFNγ. The anorexic response was intact after secondary exposure, but absent after a third injection, which was still able to elevate corticosterone. It is unlikely that IL-1 mediated the persistent effects on corticosterone, since this was increased in groups lacking corticosterone elevations. Similarly, TNFα was only modestly elevated under repeated SEA conditions that elevated plasma corticosterone. This attenuation appeared to be inversely related to the levels of IL-10, the production of which incrementally rose with each successive injection. In conclusion, repeated exposure to SEA activates the HPA axis and alters behavior. However, there may be dissociation between the behavioral and endocrine effects of SEA with increased SEA exposure. Furthermore, it is possible that while TNFα was previously shown to be important in response to acute SEA-induced HPA axis activation, further exposure to SEA elicits other cytokines that may exert neuromodulatory effects through sensitization and/or synergistic mechanisms.

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“…It has long been known that S. aureus releases factors with immunomodulatory functions, such as enterotoxins, which act as superantigens and stimulate strong proliferation of both CD4 + and CD8 + T cells through specific interactions with the Vb-chains of their TCRs (7). Exposure to superantigens, such as staphylococcal enterotoxin B, was shown to cause memory cells to become refractory to specific agonist peptide Ag (8). The surface-exposed protein A of S. aureus interacts with soluble and membrane-bound Igs encoded by the IgH V region (V H ) clan III genes, thereby inducing a largescale deletion of B-1 cell clones that can result in devastating defects on the function of the immune system (9).…”

mentioning

confidence: 99%

A Major Role for Myeloid-Derived Suppressor Cells and a Minor Role for Regulatory T Cells in Immunosuppression during Staphylococcus aureus Infection

Tebartz

Horst

Sparwasser

et al. 2015

The Journal of Immunology

138

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Staphylococcus aureus can cause difficult-to-treat chronic infections. We recently reported that S. aureus chronic infection was associated with a profound inhibition of T cell responses. In this study, we investigated the mechanisms responsible for the suppression of T cell responses during chronic S. aureus infection. Using in vitro coculture systems, as well as in vivo adoptive transfer of CFSE-labeled OT-II cells, we demonstrated the presence of immunosuppressive mechanisms in splenocytes of S. aureus–infected mice that inhibited the response of OT-II cells to cognate antigenic stimulation. Immunosuppression was IL-10/TGF-β independent but required cell–cell proximity. Using DEREG and Foxp3gfp mice, we demonstrated that CD4+CD25+Foxp3+ regulatory T cells contributed, but only to a minor degree, to bystander immunosuppression. Neither regulatory B cells nor tolerogenic dendritic cells contributed to immunosuppression. Instead, we found a significant expansion of granulocytic (CD11b+Ly6G+Ly6Clow) and monocytic (CD11b+Ly6G−Ly6Chigh) myeloid-derived suppressor cells (MDSC) in chronically infected mice, which exerted a strong immunosuppressive effect on T cell responses. Splenocytes of S. aureus–infected mice lost most of their suppressive activity after the in vivo depletion of MDSC by treatment with gemcitabine. Furthermore, a robust negative correlation was observed between the degree of T cell inhibition and the number of MDSC. An increase in the numbers of MDSC in S. aureus–infected mice by adoptive transfer caused a significant exacerbation of infection. In summary, our results indicate that expansion of MDSC and, to a minor degree, of regulatory T cells in S. aureus–infected mice may create an immunosuppressive environment that sustains chronic infection.

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Staphylococcal enterotoxin B induces anergy to conventional peptide in memory T cells

Cited by 19 publications

References 42 publications

Differences in Signaling Molecule Organization between Naive and Memory CD4+ T Lymphocytes

Differences in Signaling Molecule Organization between Naive and Memory CD4+ T Lymphocytes

Relationship of varying patterns of cytokine production to the anorexic and neuroendocrine effects of repeated Staphylococcal enterotoxin A exposure☆

A Major Role for Myeloid-Derived Suppressor Cells and a Minor Role for Regulatory T Cells in Immunosuppression during Staphylococcus aureus Infection

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