cell subpopulations
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2022 ◽  
Vol 142 ◽  
pp. 50-62
Author(s):  
Payal Damani-Yokota ◽  
Fengqiu Zhang ◽  
Alexandria Gillespie ◽  
Haeree Park ◽  
Amy Burnside ◽  
...  

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 412
Author(s):  
Julio Flores-Gonzalez ◽  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Ivette Buendia-Roldan ◽  
Beda Islas-Muñoz ◽  
...  

Human herpesvirus-8 infection (HHV-8) is the causative agent of Kaposi sarcoma (KS) and is highly prevalent among people living with HIV (KS/HIV). It has been reported that valganciclovir (VGC) reduces HHV-8 replication in KS/HIV patients. However, currently it is unclear if VGC modifies the frequency and induces changes in markers of immune regulation of immune cells necessary to eliminate HHV8-infected cells, such as Natural Killer (NK) and NK T cells (NKT). This study evaluated the effect of VGC used as antiviral HHV8 therapy in KS patients on the frequency of NK and NKT subpopulations based on the CD27 and CD57 expression, and the immunosenescence markers, PD-1 and KLRG1. Twenty KS/HIV patients were followed-up at baseline (W0), 4 (W4), and 12 weeks (W12) of the study protocol. Among them, 10 patients received a conventional treatment scheme (CT), solely antiretroviral therapy (ART), and 10 patients received a modified treatment regime (MT), including VGC plus ART. In both groups, bleomycin/vincristine was administrated according to the treating physician’s decision. The soluble levels of IL-15, PD-L1, PD-L2, and E-cadherin were quantified across the follow-up. Our results showed that the higher IL-15 levels and lower NK frequencies cells in KS/HIV patients reach almost normal values with both treatments regimes at W12. CD27+ NK and NKT cell frequencies increased since W4 on KS/HIV patients with MT. Furthermore, PD-1 expression decreased while KLRG1 increased on NK and NKT subpopulations at W12, and it is accompanied by increased PD-L1 plasma level since W4. Our study highlights the disruption of NK and NKT subpopulations in patients with KS/HIV and explores VGC treatment’s contribution to immune reconstitution during the first weeks of treatment.


Author(s):  
Barbara Fazekas ◽  
Senthilkumar Alagesan ◽  
Luke Watson ◽  
Olivia Ng ◽  
Callum M. Conroy ◽  
...  

Summary Mesenchymal stromal cells (MSCs) ameliorate pre-clinical sepsis and sepsis-associated acute kidney injury (SA-AKI) but clinical trials of single-dose MSCs have not indicated robust efficacy. This study investigated immunomodulatory effects of a novel MSC product (CD362-selected human umbilical cord-derived MSCs [hUC-MSCs]) in mouse endotoxemia and polymicrobial sepsis models. Initially, mice received intra-peritoneal (i.p.) lipopolysaccharide (LPS) followed by single i.p. doses of hUC-MSCs or vehicle. Next, mice underwent cecal ligation and puncture (CLP) followed by intravenous (i.v.) doses of hUC-MSCs at 4 h or 4 and 28 h. Analyses included serum/plasma assays of biochemical indices, inflammatory mediators and the AKI biomarker NGAL; multi-color flow cytometry of peritoneal macrophages (LPS) and intra-renal immune cell subpopulations (CLP) and histology/immunohistochemistry of kidney (CLP). At 72 h post-LPS injections, hUC-MSCs reduced serum inflammatory mediators and peritoneal macrophage M1/M2 ratio. Repeated, but not single, hUC-MSC doses administered at 48 h post-CLP resulted in lower serum concentrations of inflammatory mediators, lower plasma NGAL and reversal of sepsis-associated depletion of intra-renal T cell and myeloid cell subpopulations. Hierarchical clustering analysis of all 48-h serum/plasma analytes demonstrated partial co-clustering of repeated-dose hUC-MSC CLP animals with a Sham group but did not reveal a distinct signature of response to therapy. It was concluded that repeated doses of CD362-selected hUC-MSCs are required to modulate systemic and local immune/inflammatory events in polymicrobial sepsis and SA-AKI. Inter-individual variability and lack of effect of single dose MSC administration in the CLP model are consistent with observations to date from early-phase clinical trials. Graphical Abstract


2022 ◽  
Author(s):  
Liwei Yang ◽  
Jesse Liu ◽  
Revanth Reddy ◽  
Jun Wang

The identification and characterization of T cell subpopulations is critical to reveal cell development throughout life and immune responses to environmental factors. Next-generation sequencing technologies have dramatically advanced the single-cell genomics and transcriptomics for T cell classification. However, gene expression is often not correlated with protein expression, and immunotyping is mostly accepted in the protein format. Current single-cell proteomics technologies are either limited in multiplex capacity or not sensitive enough to detect the critical functional proteins. Herein we present a cyclic multiplex in situ tagging (Cyclic MIST) technology to simultaneously measure 465 proteins, a scale of >10 times than similar technologies, in single cells. Such a high multiplexity is achieved by reiterative staining of the single cells coupled with a MIST array for detection. This technology has been thoroughly validated through comparison with flow cytometry and fluorescence immunostaining techniques. Both THP1 and CD4+ T cells are analyzed by the Cyclic MIST technology, and over 300 surface markers have been profiled to classify the subpopulations. This represents the most comprehensive mapping of the diversity of immune cells at the protein level. With additional information from intracellular proteins of the same single cells, our technology can potentially facilitate mechanistic studies of immune responses, particularly cytokine storm that results in sepsis.


Fishes ◽  
2022 ◽  
Vol 7 (1) ◽  
pp. 12
Author(s):  
Fabio Sarais ◽  
Ruth Montero ◽  
Sven Ostermann ◽  
Alexander Rebl ◽  
Bernd Köllner ◽  
...  

The teleost head kidney is a highly relevant immune organ, and myeloid cells play a major role in this organ’s innate and adaptive immune responses. Because of their complexity, the early phases of the innate immune reaction of fish against bacteria are still poorly understood. In this study, naïve rainbow trout were stimulated with inactivated A. salmonicida and sampled at 12 h, 24 h and 7 d poststimulation. Cells from the head kidney were magnetically sorted with a monoclonal antibody mAB21 to obtain one (MAb21-positive) fraction enriched with myeloid cells and one (MAb21-negative) fraction enriched with lymphocytes and thrombocytes. The gene expression pattern of the resulting cell subpopulations was analysed using a panel of 43 immune-related genes. The results show an overall downregulation of the complement pathway and cytokine production at the considered time points. Some of the selected genes may be considered as parameters for diagnosing bacterial furunculosis of rainbow trout.


2022 ◽  
Vol 11 (2) ◽  
pp. 291
Author(s):  
Anna Tylutka ◽  
Barbara Morawin ◽  
Artur Gramacki ◽  
Agnieszka Zembron-Lacny

Age-related immune deficiencies increase the risk of comorbidities and mortality. This study evaluated immunosenescence patterns by flow cytometry of naïve and memory T cell subpopulations and the immune risk profile (IRP), expressed as the CD4/CD8 ratio and IgG CMV related to comorbidities. The disproportions in naïve and memory T cells, as well as in the CD4/CD8 ratio, were analysed in 99 elderly individuals (71.9 ± 5.8 years) diagnosed with hypertension (n = 51) or without hypertension (n = 48), using an eight-parameter flow cytometer. The percentage of CD4+ T lymphocytes was significantly higher in hypertensive than other individuals independently from CMV infections, with approximately 34% having CD4/CD8 > 2.5, and only 4% of the elderly with hypertension having CD4/CD8 < 1. The elderly with a normal BMI demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5, while overweight and obese participants showed a tendency to an inverted CD4/CD8 ratio. CD4/CD8 ratio increased gradually with age and reached the highest values in participants aged >75 years. The decline in CD4+ naïve T lymphocytes was more prominent in IgG CMV+ men when compared to IgG CMV+ women. The changes in naïve and memory T lymphocyte population, CD4/CD8, and CMV seropositivity included in IRP are important markers of health status in the elderly that are dependent on hypertension.


Author(s):  
Yafei Rao ◽  
Xiaoyan Gai ◽  
Yanqing Le ◽  
Jing Xiong ◽  
Yujia Liu ◽  
...  

AimSmoker COPD patients with chest radiological signs of prior tuberculosis (TB) showed more severe lung damage, but the mechanisms remain unclear. Emerging evidence has implicated NK cells in the pathogenesis of both COPD and TB. The purpose of this study was to delineate the profile and cytokine production of NK-cell subpopulations and their immunometabolic changes after exposure to both cigarette smoke (CS) and Mycobacterium tuberculosis(MTB).MethodsWe profiled NK-cell subpopulations in terms of percentage and cytokine production by flow cytometry in smoker patients with pulmonary TB (PTB). In an in vitro coexposure model, we investigated proinflammatory cytokine production, glycolytic influx, and oxidative phosphorylation of NK cells under CS extract (CSE) and PPD costimulation.ResultsPeripheral blood NK cells in smoker patients with active PTB (CS+PTB group) showed altered proportion of subpopulations and excessive proinflammatory cytokine expressions. In vitro, CSE- and PPD-coexposed NK-92 cells displayed enhanced proinflammatory cytokine production, concurrent with decreased glycolytic influx and oxidative phosphorylation.ConclusionSmoker patients with active PTB showed enhanced proinflammatory cytokine expression within altered NK cell subpopulations. CSE and PPD coexposure induced heightened cytokine production concurrent with impaired cell metabolism in NK cells. These novel data suggest a potential role of NK cells in the pathogenesis of lung injury in subjects with coexposure to CS and TB.


2022 ◽  
Vol 12 ◽  
Author(s):  
Elin Rönnberg ◽  
Daryl Zhong Hao Boey ◽  
Avinash Ravindran ◽  
Jesper Säfholm ◽  
Ann-Charlotte Orre ◽  
...  

BackgroundImmunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed.MethodsHuman lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen™ kit. Markers that exhibited high variance were selected for additional analyses to reveal whether they were correlated and whether discrete mast cell subpopulations were discernable.ResultsWe identified the expression of 102 surface markers on human lung mast cells, 23 previously not described on mast cells, of which several showed high continuous variation in their expression. Six of these markers were correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers was also correlated with the size and granularity of mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution.ConclusionsLEGENDScreen analysis identified more than 100 cell-surface markers on mast cells, including 23 that, to the best of our knowledge, have not been previously described on human mast cells. The comprehensive expression profiling of the 332 surface markers did not identify distinct mast cell subpopulations. Instead, we demonstrate the continuous nature of human lung mast cell heterogeneity.


2022 ◽  
Author(s):  
Hahn Nahmgoong ◽  
Yong Geun Jeon ◽  
Eun Seo Park ◽  
Yoon Ha Choi ◽  
Sang Mun Han ◽  
...  

Author(s):  
Wenhong Hou ◽  
Li Duan ◽  
Changyuan Huang ◽  
Xingfu Li ◽  
Xiao Xu ◽  
...  

Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative medicine and the treatment of autoimmune disorders. Comparing MSCs from different tissues at the single-cell level is fundamental for optimizing clinical applications. Here we analyzed single-cell RNA-seq data of MSCs from four tissues, namely umbilical cord, bone marrow, synovial tissue, and adipose tissue. We identified three major cell subpopulations, namely osteo-MSCs, chondro-MSCs, and adipo/myo-MSCs, across all MSC samples. MSCs from the umbilical cord exhibited the highest immunosuppression, potentially indicating it is the best immune modulator for autoimmune diseases. MSC subpopulations, with different subtypes and tissue sources, showed pronounced differences in differentiation potentials. After we compared the cell subpopulations and cell status pre-and-post chondrogenesis induction, osteogenesis induction, and adipogenesis induction, respectively, we found MSC subpopulations expanded and differentiated when their subtypes consist with induction directions, while the other subpopulations shrank. We identified the genes and transcription factors underlying each induction at the single-cell level and subpopulation level, providing better targets for improving induction efficiency.


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