RATIONALE: Human olfactory mucosa-derived mesenchymal stem cells (hOM-MSCs) are promising for treatment of immune diseases. The immunomodulatory activities of hOM-MSCs are partially ascribed to CD4 + T and B-lymphocytes, macrophages, and dendritic cells. The effect of the hOM-MSCs on function of CD8 + cytotoxic lymphocytes (CTLs) and natural killer cells (NKCs) was assessed. METHODS: hOM-MSC were generated from biopsies of patients (n53) with non-inflammatory diseases of the nasal cavity. Peripheral blood mononuclear cells (PBMCs) (n57) were cultured over hOM-MSCs in 10:1 ratio for 3 days. Expression of perforin, granzyme B and CD107a were analyzed in both CTLs and NKCs subsets. Jurkat cells were used as target cells. PBMCs and Jurkat were co-cultured in a 5:1 ratio for 2 h. Necrosis and apoptosis were detected by Annexin V (FITC) / To-PRO-3 staining. RESULTS: The hOM-MSCs reduced granzyme B and perforin expression in NKCs, but not in CTLs. The hOM-MSCs suppressed both spontaneous and tumor cell-stimulated degranulation detected by CD107a expression in both CTLs and NKCs. The Viability assay showed that hOM-MSC-treated PBMCs possessed reduced ability to induce apoptosis in target cells (MSCs-treated group-22.2 [range 18.2-27.3]%, control-13.3 [range 12.0-15.4]%; p50.02). CONCLUSIONS: hOM-MSCs suppressed cytotoxic functions of CTLs and NKCs affecting expression of perforin, granzyme B, CD107a, which eventually led to the reduced ability to induce apoptosis in target tumor cells. The development of MSC-based cell therapy may be useful for diseases associated with excessive cytotoxicity.
The prevalence of asthma and allergic airway diseases has increased since the 1960s. The use of dishwasher and household detergents showed a similar trend, leading us to hypothesize that increased exposure to detergents might contribute to development of allergic diseases. The goal of this project was to test this hypothesis by using in vitro and in vivo models. METHODS: We exposed normal human bronchial epithelial (NHBE) cells that overexpress the IL-33 gene to sodium dodecyl benzene sulfonate (SDBS) as a model for detergent. Various pharmacologic agents were used to dissect the mechanisms for IL-33 release. SDBS was also administered intranasally (i.n.) to na€ ıve BALB/c mice. RESULTS: Exposure to SDBS induced IL-33 release from NHBE cells. The dose-response curve was bell-shaped, and the maximum effect was observed at a 3-fold lower concentration (i.e. 50 mg/ml) than the critical micelle concentration for SDBS. At this concentration, more than 90% of NHBE cells were alive, released ATP extracellularly and showed increase in intracellular calcium concentration. IL-33 release was abolished by treating the cells with purinergic receptor antagonists or oxygen radical scavengers or by chelating extracellular calcium. Moreover, the levels of type 2 cytokines in lung homogenates were increased in mice exposed to SDBS in vivo. CONCLUSIONS: Exposure of airway epithelial cells to a low concentration of detergents induces active release of IL-33 likely through the pathway(s) involved in cellular stress responses. Detergents may dysregulate the homeostasis of epithelium and promote development of type 2 immune responses to environmental allergens.
RATIONALE: Little is known about function and dynamic changes in the myeloid compartment in COVID-19 patients. This study analyzes the myeloid cells subsets counts in COVID-19 patients. METHODS: 57 patients with PCR and chest CT confirmed diagnosis of COVID-19 pneumonia were included in the study. Patients were divided into 2 groups: severe/critical (S/C) patients (n518) which were treated in ICU and required IMV; and moderate (M) patients (n539) which received oxygen support through nasal mask. Blood samples from 19 healthy donors (HD) controls were also used. Granulocytic and monocytic myeloidderived suppressor cells (G/M-MDSC), monocytes (Mon), myeloid and plasmacytoid dendritic cells (mDC and pDC) were assayed using Attune NxT flow cytometer. Nonparametric statistics were used.
RATIONALE: Measles vaccine is given as part of MMR vaccine series in 2 separate doses, achieving approximately 95-99% seroconversion rate. Determining sufficient clinical response to measles vaccine in at-risk population (e.g. healthcare workers) has not been established. METHODS: Retrospective chart review was performed on three Kings County Hospital Center employees identified as having negative measles titers, despite repeated vaccination with MMR. RESULTS: Three healthcare workers were identified with negative titers to measles during pre-employment laboratory analysis. All three cases had normal WBC counts/differential (mean WBC counts 6.1 K/uL), negative hepatitis panel and positive HepBs Ab titers. Two cases were female employees who each received a total of 4 MMR doses, with the last doses given on 12/2012 and 2/2014, respectively. Their MMR titers were respectively measured on 4/2015 and 8/2014, showing positive mumps and rubella IgG titers yet negative measles IgG. The third case involved a male employee who received a total of 6 doses of MMR, with the last dose given on 12/2013. His MMR titers were measured on 5/2014, similarly showing positive mumps and rubella IgG titers; however, measles IgG titer was equivocal-with negative repeat measles IgG on 6/2014. His serum CD3/CD4/CD8/B & T cell counts were normal. There was no history of immunodeficiency or recurrent infections in all three cases. CONCLUSIONS: We identified three cases of negative measles titers in otherwise healthy healthcare workers after repeated vaccination. Consensus to further evaluation of otherwise healthy individuals with negative laboratory vaccine response has not been established.
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