Anette Sundstedt

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Members of the suppressor of cytokine signaling (SOCS) family were discovered as negative regulators of cytokine signaling by inhibition of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) pathway. Among them, cytokine-induced Src homology 2 (SH2) protein (CIS) was found to inhibit the interleukin 3- and erythropietin-mediated(More)
Regulatory CD4(+) T cells were induced in the Tg4 TCR transgenic mouse specific for the N-terminal peptide (Ac1-9) of myelin basic protein by intranasal administration of a high-affinity MHC-binding analog (Ac1-9[4Y]). Peptide-induced tolerant cells (PItol) were anergic, failed to produce IL-2, but responded to Ag by secretion of IL-10. PItol cells were(More)
We have recently demonstrated that the superantigen staphylococcal enterotoxin A (SEA) conjugated to colon-carcinoma-reactive monoclonal antibodies (MAbs) directs T cells to lyse human colon-carcinoma cells, representing a potential novel tumor therapy. To further analyze the mechanism of antitumor effects of superantigen-activated T cells, we compared the(More)
The response of mouse T cells to the superantigen staphylococcal enterotoxin A (SEA) requires 1000-fold higher concentrations compared to human T cells. In order to develop a sensitive model for SEA studies in mice, the immunopharmacology has been studied in T-cell receptor (TcR) V beta 3 transgenic (TGV beta 3) and non-transgenic (non-TG) C57Bl/6 mice. The(More)
The transcriptional events that control T cell tolerance are still poorly understood. To investigate why tolerant T cells fail to produce interleukin (IL)-2, we analyzed the regulation of NFkappaB-mediated transcription in CD4(+) T cells after tolerance induction in vivo. We demonstrate that a predominance of p50-p50 homodimers binding to the IL-2 promoter(More)
Injection of the superantigen staphylococcal enterotoxin A (SEA) to mice rapidly elicits production of the Th1-related pro-inflammatory cytokines IL-2, TNF, and IFN-gamma, while repeated SEA challenges transduce a hyporesponsive state characterized by T cell deletions and anergy in the remaining SEA-reactive T cells. In the present study we show that(More)
Repetitive antigen stimulation induces peripheral T cell tolerance in vivo. It is not known, however, whether multiple stimulations merely suppress T cell activation or, alternatively, change the transcriptional program to a distinct, tolerant state. In this study, we have discovered that STAT3 and STAT5 were activated in response to antigen stimulation in(More)
Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research(More)
In this study we explored the possibility of improving the anti-tumor potency of tumor-targeted superantigens (TTS) by combination treatment with interferon-alpha (IFN-alpha). TTS utilizes the powerful T cell activating property of the superantigen staphylococcal enterotoxin A (SEA) in fusion with an anti-tumor Fab-fragment to target this T cell activity(More)
Bacterial superantigens bind to major histocompatibility complex (MHC) class II and subsequently activate both CD4+ and CD8+ T lymphocytes expressing certain T-cell receptor (TCR)-Vbeta chains. In response to superantigen exposure these subsets proliferate, produce large amounts of proinflammatory cytokines and in addition CD8+ cytotoxic T lymphocytes (CTL)(More)