Effective immunotherapy for type 1 diabetes (T1D) relies on active induction of peripheral tolerance. Myeloid-derived suppressor cells (MDSCs) play a critical role in suppressing immune responses in various pathologic settings via multiple mechanisms, including expansion of regulatory T cells (Tregs). In this study, we investigated whether MDSCs could act as APCs to induce expansion of Ag-specific Tregs, suppress T cell proliferation, and prevent autoimmune T1D development. We found that MDSC-mediated expansion of Tregs and T cell suppression required MHC-dependent Ag presentation. A murine T1D model was established in INS-HA/RAG−/− mice in which animals received CD4-HA-TCR transgenic T cells via adoptive transfer. We found a significant reduction in the incidence of diabetes in recipients receiving MDSC plus HA, but not OVA peptide, leading to 75% diabetes-free mice among the treated animals. To test further whether MDSCs could prevent diabetes onset in NOD mice, nondiabetic NOD/SCID mice were injected with inflammatory T cells from diabetic NOD mice. MDSCs significantly prevented diabetes onset, and 60% of MDSC-treated mice remained diabetes free. The pancreata of treated mice showed significantly lower levels of lymphocyte infiltration in islet and less insulitis compared with that of the control groups. The protective effects of MDSCs might be mediated by inducing anergy in autoreactive T cells and the development of CD4+CD25+Foxp3+ Tregs. Thist study demonstrates a remarkable capacity of transferred MDSCs to downregulate Ag-specific autoimmune responses and prevent diabetes onset, suggesting that MDSCs possess great potential as a novel cell-based tolerogenic therapy in the control of T1D and other autoimmune diseases.
Background: Acute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed. Methods: We retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared. Results: A total of 442 patients were enrolled. Patients with positive viral detection (N Z 311) had a significantly lower rate of leukocytosis (p Z 0.03), less evidence of bacterial infection (p Z 0.004), and shorter duration of hospitalization (p Z 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups.The most commonly identified virus was human rhinovirus. About 27% (n Z 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was Journal of Microbiology, Immunology and Infection (2019) 52, 902e910 independently associated with multiple viral infections (p Z 0.022), respiratory syncytial virus (RSV) infection (p Z 0.001) and longer hospitalization duration (p Z 0.011). Conclusion: Multiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.
The first sentence of the left-hand column of p 1753 should be "No characteristic compound for nitrofurazone metabolite is given under EU legislation, and recent development methods for nitrofuran analysis still utilize SEM as marker residue for nitrofurazone abuse."
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