0000000000173707
AUTHOR
Ortwin Rott
A Superantigen as Virulence Factor in an Acute Bacterial Infection
This study addresses the role of a bacterial superantigen as a potential virulence factor during an acute systemic infection. BALB/c mice were intravenously infected with a recombinant Staphylococcus aureus strain capable of producing plasmid-encoded staphylococcal enterotoxin B (SEB) or with the SEB plasmid-deficient parental strain. Infection with SEB-producing bacteria resulted in an initial expansion and subsequent decrease of circulating V beta 8+ T lymphocytes. This numeric decrease was accompanied by a SEB-specific state of hyporesponsiveness of splenic T cells. In parallel with SEB-triggered unresponsiveness of a large proportion of T lymphocytes, a weakening of the overall T cell r…
Macrophages are dispensable for superantigen-mediated stimulation and anergy induction of peripheral T cells in vivo.
Bacterial superantigens provoke T lymphocyte activation by cross-linking the variable part of the T cell receptor (TCR) beta-chain with MHC class II molecules on antigen-presenting cells. Although the molecular mechanisms of this interaction are well characterized, the in vivo accessory cell requirements for this stimulation of T lymphocytes by bacterial superantigens remain unknown. In the present study we have addressed the role of splenic macrophages in the activation of V beta 8+ peripheral T cells by staphylococcal enterotoxin B (SEB) in BALB/c mice. SEB-triggered clonal expansion and subsequent induction of unresponsiveness of both CD4+ and CD8+ T cells were investigated in naive anim…
Cortical neurons selectively inhibit MHC class II induction in astrocytes but not in microglial cells.
Astrocytes have been shown to act as potent accessory cells for MHC class II-restricted T cell responses in vitro after treatment with interferon-gamma. In contrast, even under conditions of severe central nervous system (CNS) inflammation, they seem to express little, if any, class II molecules in vivo. Thus the role of astroglial cells as accessory cells in immune responses in the CNS remains to be determined. We have studied neuron--glia interactions with respect to induction of MHC class II molecules. Surprisingly, in a co-culture system, viable neurons inhibited the induction of class II restriction elements on astrocytes. This effect was only observed when neurons had contact to astro…
Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1- but not type 2-associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats
The phosphodiesterase inhibitor pentoxifylline (POX), which is known to have pharmacological effects in animal models of multiorgan failure and endotoxin-mediated shock, was tested for its immunosuppressive potential on T lymphocyte activation in vitro and in vivo. POX was found to have a profound inhibitory effect on both mitogen- and antigen-induced proliferation of CD4+ T cells in vitro. This inhibitory activity of the drug could be reproduced by treating T lymphocytes with cAMP analogues during stimulation. Responses of repeatedly in vitro stimulated cells were much more strongly inhibited by the drug and by cAMP analogues than responses of fresh resting lymphocytes. Furthermore, POX co…
Protection from experimental allergic encephalomyelitis by application of a bacterial superantigen
Certain bacterial and viral T cell stimulating proteins ('superantigens') are known to be very potent activators of T cells with certain V beta receptors. When applied in vivo these molecules induce anergy in those T cells responding to them. In this study we have investigated the influence of staphylococcal enterotoxins (SE) on myelin basic protein (MBP)-specific T cells in Lewis rats. As MBP-specific T cells in rats belong exclusively to the V beta 8.2+ CD4+ subset, the induction of experimental allergic encephalomyelitis (EAE) allows for an estimation of the functional state of the respective V beta-bearing T cells after enterotoxin-induced activation. In vitro, various MBP-specific T ce…
Interleukin-6 production in "normal" and HTLV-1 tax-expressing brain-specific endothelial cells.
Abnormal cytokine production can contribute in many instances to the development of pathology. Our study focuses on the regulation of interleukin (IL)-6 production in vitro in brain-specific endothelial cells (BEC) under physiological conditions and in a model of human T leukemia virus-1 (HTLV-1) infection. IL-6 production was strongly up-regulated in a dose-dependent mode upon exposure to recombinant IL-1 beta, although nearly not detectable in unstimulated BEC. This induction of IL-6 production could be achieved by reagents known to increase intracellular levels of cAMP, such as forskolin, prostaglandin E or pentoxifylline. Furthermore, transcription and production of IL-6 was inducible b…