PubMed · 2562905
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K Bottomly, C A Janeway. 1989-01-05. Antigen presentation by B cells.. https://doi.org/10.1038/337024a0
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We found that human fetal astrocytes (HFA) are able to support superantigen (SAG) staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1)-induced activation of immediately ex vivo allogenic human CD4 T cells. Using radiolabelled toxins, we demonstrate that both SEB and TSST-1 bind with high affinity to MHC class II antigen expressing astrocytes; binding is displaceable with excess cold toxin. Competition experiments further indicate that TSST-1 and SEB at least partially compete with each other for binding to astrocytes suggesting they bind to the same HLA-DR region on these cells. Our study supports the hypothesis that SAG would be capable of stimulating immune responses within the human CNS and contribute to persistence or recurrence of inflammatory responses within this compartment.
Pro-inflammatory cytokines are important mediators in tissue responses to a wide range of endogenous (e.g. autoantigens) and exogenous (e.g. infections, wounds, biomaterials) stimuli. The complex interactions taking place between different cell types in such processes are difficult to examine in vivo. Here we studied the effect of human monocytes on thyroid epithelial cells co-cultured in bicameral chambers. Freshly isolated monocytes (1x10(6)/ml) added to the basal compartment reduced the transepithelial resistance (from 300-600 to <100 Omega.cm(2)) and caused a disruption of the tight junctions in apically grown thyrocyte monolayers after co-culture for 24 h. The barrier function was further attenuated by monocytes exposed to lipopolysaccharide (10 microg/ml) or polystyrene microspheres (size: 3 microm; 1x10(7)/ml). Loss of transepithelial resistance was accompanied by release of interleukin 1alpha (maximally 550 pg/ml) from the monocytes. Conversely, the resistance remained high when co-cultures were simultaneously incubated with neutralizing anti-human interleukin 1alpha antibodies. The results show that the integrity of cultured thyroid epithelium is impaired by monocytes without requirement of direct cell-to-cell contact. This action, mediated by interleukin-1alpha, suggests a mechanism by which hidden (lumenal) autoantigens might be exposed to interstitial antigen-presenting cells in autoimmune thyroid disease. In perspective, the model provides a tool in which humoral and cell-cell dependent processes generated by bioactive agents and particulate materials, for instance, during the healing and repair of tissue around biomaterials and hybrid implants, can be selectively examined.
Staphylococcus aureus bacteria utilize an extensive array of molecular countermeasures to manipulate the defensive microenvironment of the infected host and colonize potentially any tissue. The secreted polypeptides referred to as superantigens are unique among these countermeasures, because they target the multireceptor communication between T cells and antigen-presenting cells that is fundamental to initiating pathogen-specific immune clearance. Superantigens play a critical role in toxic-shock syndrome and food poisoning, yet their function in routine infections is not well understood. While an association of superantigens with cases of human autoimmune disease seems tantalizing, convincing data are not yet available. Blocking antigen-specific T-cell recognition is the primary evolutionary driving force behind superantigen selection, whereas superantigen-specific pathologies are by-products that are apparent only under select conditions.