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The Notch signaling pathway is an evolutionarily conserved cell signaling system present in most multicellular organisms, as it controls cell fate specification by regulating cell proliferation, differentiation, apoptosis, and survival. Regulation of the Notch signaling pathway can be achieved at multiple levels. Notch proteins are involved in lineage fate decisions in a variety of tissues in various species. Notch is essential for T lineage cell differentiation including T versus B and αβ versus γδ lineage specification. In this paper, we discuss Notch signaling in normal T-cell maturation and differentiation as well as in T-cell acute lymphoblastic lymphoma/leukemia. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics—first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGFβ, CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM. [ABSTRACT FROM AUTHOR]

Background. The mediators produced by CD4+ T lymphocytes are involved in the pathogenesis of aneurysmal lesions in abdominal aortic aneurysm (AAA) patients. The aim of this study was to identify and characterize the CD4+ T cell subsets involved in human AAA. Methods. The CD4+ T cell subsets in 30 human aneurysmal lesions were determined using flow cytometry (FC) and immunohistochemistry (IHC). The peripheral blood mononuclear cells (PBMCs) from patients with AAA were also analyzed by FC and compared with control subjects. Results. Human aneurysmal lesions contained IFN-γ, IL-12p35, IL-4, IL-23p19, IL-17R, and IL-22 positive cells. PBMCs from AAA patients had higher expression levels of IFN-γ, TNF-α, IL-4, and IL-22 when compared to controls. Conclusions. Our results show the presence of TH1, TH2, TH17, and TH22 subsets in aneurysmal lesions of AAA patients and suggest that these cells may be mainly activated in situ, where they can induce tissue degradation and contribute to the pathogenesis of AAA. [ABSTRACT FROM AUTHOR]

We investigate the global dynamics of an HIV infection model with two classes of target cells and multiple distributed intracellular delays. The model is a 5-dimensional nonlinear delay ODEs that describes the interaction of the HIV with two classes of target cells, CD4+ T cells and macrophages. The incidence rate of infection is given by saturation functional response. Themodel has two types of distributed time delays describing time needed for infection of target cell and virus replication. This model can be seen as a generalization of several models given in the literature describing the interaction of the HIV with one class of target cells, CD4+ T cells. Lyapunov functionals are constructed to establish the global asymptotic stability of the uninfected and infected steady states of the model. We have proven that if the basic reproduction number R0 is less than unity then the uninfected steady state is globally asymptotically stable, and if R0 > 1 then the infected steady state exists and it is globally asymptotically stable. [ABSTRACT FROM AUTHOR]