The engagement of the 4‐1BB (CD137) co‐stimulatory pathway promotes the activation and proliferation of conventional CD4+ T and CD8+ T cells, but the role of 4‐1BB co‐stimulation in CD4+ CD25+ regulatory T cells (Treg) is less clear. In particular, whether 4‐1BB stimulation affects the expression of Foxp3, a master gene for Treg, is unknown. This study demonstrates that co‐stimulation of 4‐1BB engaged by an agonistic antibody promotes the proliferation of Treg in a dependent manner of low‐concentration interleukin‐2 in vitro. The 4‐1BB‐expanded Treg maintain Foxp3 expression and their ability to suppress conventional CD4+ T cells and their feature to produce no interleukin‐2. However, the 4‐1BB‐expanded Treg produce increased levels of interferon‐γ, whose significance is unknown. Thus, 4‐1BB co‐stimulation plays a role in the expansion of functional CD4+ CD25+ Treg cells without adversely affecting their suppressive activity.
The energy spectrum of cosmic Hydrogen and Helium nuclei has been measured below the so-called “knee” by using a hybrid experiment with a wide field-of-view Cherenkov telescope and the Resistive Plate Chamber (RPC) array of the ARGO-YBJ experiment at 4300 m above sea level. The Hydrogen and Helium nuclei have been well separated from other cosmic ray components by using a multi-parameter technique. A highly uniform energy resolution of about 25% is achieved throughout the whole energy range (100–700 TeV). The observed energy spectrum is compatible with a single power law with index γ=−2.63±0.06.
Tumour necrosis factor-a-induced protein-8 like-2 (TIPE2) is a newly identified immune negative regulator. The abnormal expression of TIPE2 has been found in several human inflammatory diseases. However, the expression level and clinical significance of TIPE2 in childhood asthma remain unclear. In this study, we detected TIPE2 expression in peripheral blood mononuclear cells (PBMC) from 42 children with asthma and 39 healthy controls by RT-PCR, qRT-PCR and Western blot. We also detected the levels of serum total immunoglobulin E (IgE), eosinophil (EO), interleukin-4 (IL-4) and interferon-c (IFN-c) and analysed the correlations of TIPE2 expression with IgE, EO, IL-4 and IFN-c. The results showed that TIPE2 mRNA and protein expression were decreased in children with asthma compared with healthy controls. The levels of IgE, EO and IL-4 in the children with asthma were obviously higher than those in normal controls, while the level of IFN-c in patients with asthma was significantly lower than that in healthy subjects. Furthermore, the expression level of TIPE2 mRNA was negatively correlated with IgE, EO and IL-4. However, no statistically significant correlation was found between TIPE2 mRNA expression and serum IFN-c level. In conclusion, our data suggest that reduced TIPE2 expression may contribute to the pathogenesis of childhood asthma.
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