High‐resolution determination of human immune cell signatures from fine‐needle liver aspirates

Hengst, Julia; Theorell, Jakob; Deterding, Katja; Potthoff, Andrej; Dettmer, A; Ljunggren, Hans‐Gustaf; Wedemeyer, Heiner; Björkström, Niklas K.

doi:10.1002/eji.201445369

Cited by 24 publications

(22 citation statements)

References 12 publications

(13 reference statements)

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“…Many protocols for tissue dissociation and cell isolation use a combination of the above procedures as one technique on its own may not deliver a high cell yield and cell viability. Alternative methods such as aspiration may also be used [152]. A successful protocol depends in general on the personal experience in the laboratory.…”

Section: General Commentsmentioning

confidence: 99%

Guidelines for the use of flow cytometry and cell sorting in immunological studies^*

et al. 2017

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International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis

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Section: General Commentsmentioning

confidence: 99%

Guidelines for the use of flow cytometry and cell sorting in immunological studies^*

et al. 2017

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“…We hypothesized that the ascitic fluid in patients with decompensated cirrhosis represents a special immune environment, as its existence is linked to pathological processes. To address this, we applied a broad 21-parameter flow cytometry panel (32) as well as a multiplex cytokine assay on ascites fluid samples. The obtained FACS data were analyzed using conventional gating, and UMAP (28) was used to reduce dimensions and to identify main clusters of immune cells ( Fig.…”

Section: Immune Environment In Ascites Fluid Of Patients With Decompementioning

confidence: 99%

MAIT Cells Are Enriched and Highly Functional in Ascites of Patients With Decompensated Liver Cirrhosis

et al. 2020

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List of abbreviationsARC, alcohol related cirrhosis; HXV, hepatitis virus related cirrhosis; IFNγ, interferon γ; MELD, model for end-stage liver disease; MNC, mononuclear cells; PBMC, peripheral blood mononuclear cells; SBP, spontaneous bacterial peritonitis; TCR, T cell receptor; TNF, tumor necrosis factor. Abstract Patients with advanced liver cirrhosis have an increased susceptibility to infections. As part of the cirrhosis-associated immune dysfunction, mucosal associated invariant T (MAIT) cells, that have the capacity to respond towards bacteria, are severely diminished in circulation and liver tissue. However, MAIT cell presence and function in the peritoneal cavity, a common anatomical site for infections in cirrhosis, remain elusive. To study this, matched peripheral blood and ascites fluid were collected from 35 patients with decompensated cirrhosis, with or without spontaneous bacterial peritonitis (SBP). MAIT cell phenotype and function were analyzed using highdimensional flow cytometry and obtained data was compared to blood samples of healthy controls (n=24) and patients with compensated cirrhosis (n=11). We found circulating MAIT cells to be severely decreased in cirrhotic patients as compared to controls. In contrast, in ascites fluid, MAIT cells were significantly increased together with CD14 + CD16 + monocytes, ILCs, and NK cells. This was paralleled by elevated levels of several pro-inflammatory cytokines and chemokines in ascites fluid as compared to plasma. Peritoneal MAIT cells displayed an activated tissue-resident phenotype and this was corroborated by increased functional responses following stimulation with E. coli or lL-12 + IL-18 as compared to circulating MAIT cells. During SBP, peritoneal MAIT cell frequencies increased most among all major immune cell subsets, suggestive of active homing of MAIT cells to the site of infection. Conclusions: Despite severely diminished MAIT cell numbers and impaired phenotype in circulation, peritoneal MAIT cells remain abundant, activated, and highly functional in decompensated cirrhosis and are further enriched in SBP. This suggests that peritoneal MAIT cells could be of interest for immune intervention strategies in patients with decompensated liver cirrhosis and SBP.

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“…To determine the impact of chronic HCV-infection on the peripheral blood immune cell compartment, we assessed the major myeloid and lymphoid immune cell subsets in a cohort of HCVpatients and healthy donors by using a 23-parameter flow cytometry staining approach as previously described [24] (Supporting Information Fig. 1).…”

Section: Mait Cells Are Among the Most Severely Affected Immune Cellsmentioning

confidence: 99%

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

et al. 2016

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Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction Mucosal-associated invariant T (MAIT) cells are T cells with innate-like characteristics enriched in human liver and at mucosalCorrespondence: Dr. Niklas K. Björkström e-mail: niklas.bjorkstrom@ki.se sites [1,2]. They express a semi-invariant TCR carrying the Vα7.2 segment together with a restricted Vβ repertoire [1,2]. Upon activation, MAIT cells respond rapidly with cellular cytotoxicity as well as secretion of proinflammatory and anti-viral cytokines such * These authors contributed equally to this work. HCV is an extremely successful pathogen in that it establishes chronic infection in up to 90% of infected humans [9]. The reasons behind the failure of the human immune system to clear HCV are not fully understood but involve viral escape, CD4 and CD8 T-cell exhaustion, as well as NK-cell dysfunction [10][11][12] Until recently, pegylated IFN-α together with ribavirin was used to treat chronic HCV-infection. However, pegylated IFN-α in doses administered to patients has direct inhibitory effects on immune cells [15][16][17][18]. In the last years, treatment of HCV has undergone a revolution with the introduction of highly effective direct-acting antivirals (DAA) that rapidly eliminate the virus [19]. Thus, today the vast majority of patients clear HCV after such IFN-free treatment regimens. This remarkable outcome allows for studies on consequences on immune cell recovery following rapid pathogen removal. In such studies, it was recently shown that both HCVspecific CD8 T cell and NK-cell populations become reinvigorated following viral clearance [20][21][22][23]. However, whether MAIT cells recover upon HCV clearance remains unclear.Here, we performed a comprehensive analysis of MAIT cells in chronic HCV-infection. Specifically, we addressed whether MAIT cell recovery occurs upon HCV-clearance in patients receiving an IFN-free treatment regimen consisting of sofosbuvir and ribavirin. Strikingly, and in contrast to other immune cells, MAIT cells were not reinvigorated following successful HCV-clearance using IFNfree therapy. The results are discussed in relation to the current knowledge on human MAIT cell responses to other viral infections and in the context of immune exhaustion during chronic infections. Results and discussion MAIT cells are among the most severely affected immune cells in chronic HCV-infectionTo determine the impact of chronic HCV-infection on the peripheral blood immune cell compartment, we assessed the major myeloid and lymphoid immune cell subsets in a cohort of HCVpatients and healthy donors by using a 23-parameter flow cytometry staining approach as previously described [24] (Supporting Information Fig. 1). The major phenotype observed in chronic HCV was a severe loss of MAIT cells (Fig. 1A, B). Other immune cell alterations noted were in line with previous studies, including an increase in Tregs [25], a reduced frequency of pDCs [26], and a shift within the CD4...

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High‐resolution determination of human immune cell signatures from fine‐needle liver aspirates

Abstract: Abbreviations: FNAB: fine-needle aspiration biopsy · SNE: stochastic neighbor embedding Keywords: High-dimensional data visualization r Liver immunophenotyping r Multicolor flow cytometry

Cited by 24 publications

References 12 publications

Guidelines for the use of flow cytometry and cell sorting in immunological studies^*

Guidelines for the use of flow cytometry and cell sorting in immunological studies^*

MAIT Cells Are Enriched and Highly Functional in Ascites of Patients With Decompensated Liver Cirrhosis

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

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High‐resolution determination of human immune cell signatures from fine‐needle liver aspirates

Abstract: Abbreviations: FNAB: fine-needle aspiration biopsy · SNE: stochastic neighbor embedding Keywords: High-dimensional data visualization r Liver immunophenotyping r Multicolor flow cytometry

Cited by 24 publications

References 12 publications

Guidelines for the use of flow cytometry and cell sorting in immunological studies*

Guidelines for the use of flow cytometry and cell sorting in immunological studies*

MAIT Cells Are Enriched and Highly Functional in Ascites of Patients With Decompensated Liver Cirrhosis

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

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Guidelines for the use of flow cytometry and cell sorting in immunological studies^*

Guidelines for the use of flow cytometry and cell sorting in immunological studies^*