Cholera toxin B subunit (CTB) is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens. There is also good evidence that CTB acts as an immunosuppressant, as it is able to down-modulate human monocyte/macrophage cell line activation and to suppress Th1-type responses. In the present study, we examined the possibility that recombinant CTB (rCTB) may affect human dendritic cell (DC) functions in response to LPS stimulation and may induce the generation of DC with the capacity to generate CD4(+) regulatory T cells (Tregs). Our findings show that rCTB partially prevents the LPS-induced maturation process of monocyte-derived DC (MDDC) and decreases their IL-12 production with no relevant effect on IL-10 production. LPS-stimulated MDDC pretreated with rCTB are able to promote the induction of low proliferating T cells, which show an enhanced IL-10 production associated with a reduced IFN-gamma production and the same high levels of TGF-beta as the control. These T cells suppress proliferation of activated autologous T cells. Transwell experiments and blockade of IL-10R and TGF-beta showed that the immunomodulatory effect is mediated by soluble factors. Thus, T cells induced by rCTB-conditioned MDDC acquire a regulatory phenotype and activity similar to those described for type 1 Tregs.
Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heterogeneity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpredictable response to therapies. The major focus of the research on MS is the identification of biomarkers in biological fluids, such as cerebrospinal fluid or blood, to guide patient management reliably. Because of the difficulties in obtaining spinal fluid samples and the necessity for lumbar puncture to make a diagnosis has reduced, the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However, currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkers could radically alter the management of MS at critical phases of the disease spectrum, allowing for intervention strategies that may prevent evolution to long-term neurological disability. This article provides an overview of this research field and focuses on recent advances in blood-based biomarker research.
The percentage of LP CD4LAP+ cells is increased in active UC, showing reduced suppressor activity due to their increased proportion of intracellular IL-17 expression.
In this paper, we show that the antioxidant N-acetyl-cysteine (NAC) is capable of enhancing the adhesion properties of the epithelial cell line A431 and of the lymphocytic cells with cytotoxic activity from human peripheral blood: the natural killer (NK) cells. This effect leads to an increased efficiency of A431 cells to form a monolayer and of NK cells to kill their targets. In both cases a specific effect of NAC was found in the distribution of those molecules of the cytoskeleton which are generally involved in cell substrate and cell-to-cell contact region formation, e.g., the actin microfilaments. NAC could thus behave as a drug influencing certain cytoskeleton-dependent cell processes in a non-histotype dependent manner.
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