Interferon-c (IFN-c)-preactivated mesenchymal stem cells (MSC-c) are highly immunosuppressive but immunogenic in vivo due to their inherent expression of major histocompatibility (MHC) molecules. Here, we present an improved approach where we modified human bone marrowderived MSC with interleukin-17A (MSC-17) to enhance T cell immunosuppression but not their immunogenicity. MSC-17, unlike MSC-c, showed no induction or upregulation of MHC class I, MHC class II, and T cell costimulatory molecule CD40, but maintained normal MSC morphology and phenotypic marker expression.
SIGNIFICANCE STATEMENTMesenchymal stem cells (MSC) are potent and promising immunomodulatory cell therapy that have progressed into the clinic for allotransplantation. Cytokine modified MSC show superior immunosuppressive properties compared to unmodified MSC. In this study, we describe the enhanced immunosuppressive properties of MSC generated under the influence of the proinflammatory cytokine interleukin-17A (MSC-17) compared to interferon-gamma pre-treated MSC (MSC-c). Specifically these human MSC-17 have translational potential in transplantation protocols because they do not express MHC class II, thereby reducing their immunogenicity, in addition to avidly promote the formation of induced T regulatory cells.
Background: Chemotherapy for cancer is an intense and cyclic treatment associated with number of side-effects. The present study evaluated the effect of chemotherapy on distress, anxiety and depression.
This study was performed to find out whether ultrasound is an important adjunct to clinical and laboratory profile in diagnosing dengue fever or dengue haemorrhagic fever and to further determine whether ultrasound is useful in predicting the severity of the disease. Ultrasound was performed on 128 patients (2-9 years) with clinical suspicion of dengue fever. Serological tests were performed to confirm the diagnosis. 40 patients were serologically negative for dengue fever and later excluded from the study. Of the remaining 88 serologically positive cases, 32 patients underwent ultrasound on second to third day, repeated on fifth to seventh day of fever and in 56 patients ultrasound was done only on fifth to seventh day of fever. Of the 32 patients who underwent the study on second to third day of fever, all showed gall bladder wall thickening and pericholecystic fluid, 21% had hepatomegaly, 6.25% had splenomegaly and right minimal pleural effusion. Follow-up ultrasound on fifth to seventh day revealed ascites in 53% left pleural effusion in 22% and pericardial effusion in 28%. Of the 56 patients who underwent the study on fifth to seventh day of fever for the first time all had gall bladder wall thickening, 21% had hepatomegaly, 7% had splenomegaly, 96% had ascites, 87.5% had right pleural effusion, 66% had left pleural effusion and 28.5% had pericardial fluid. To conclude, in an epidemic of dengue, ultrasound features of thickened gall bladder wall, pleural effusion and ascites should strongly favour the diagnosis of dengue fever.
Local gene therapy-mediated expression of the immunomodulatory cytokine IL-10 has the potential to reduce the incidence of corneal graft rejection and to prolong corneal allograft survival.
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