Profiles of Immune Cell Infiltration in Carotid Artery Atherosclerosis Based on Gene Expression Data

Since immune infiltration is closely associated with the progression and prognosis of atherosclerosis, we aimed to describe the abundance of 24 immune cell types within atherosclerotic tissues. In the current study, we used the Immune Cell Abundance Identifier (ImmuCellAI), a web-based tool, to estimate the abundance of 24 immune cells based on the microarray profiles of atherosclerotic carotid artery samples to analyze the proportions and the dysregulation of immune cell types within carotid atherosclerosis. We found that atherosclerotic immune cells had a diverse landscape dominated by T cells and myeloid cells and that macrophages and dendritic cells (DCs) showed different abundance in normal and atherosclerotic tissues. Moreover, the expression of macrophages was closely related to the level of the expression of DCs and of exhausted T cells, while the expression of T-helper type 1 (Th1) cells was strongly correlated with the expression of T-helper type 2 (Th2) cells and effector memory cells. Our data confirm a distinct profile of atherosclerosis-infiltrating immune cell subpopulations, which may inspire an immunological direction for research on atherosclerosis.

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Knowledge-based classification of fine-grained immune cell types in single-cell RNA-Seq data with ImmClassifier

10.1101/2020.03.23.002758 ◽

2020 ◽

Author(s):

Xuan Liu ◽

Sara J.C. Gosline ◽

Lance T. Pflieger ◽

Pierre Wallet ◽

Archana Iyer ◽

...

Keyword(s):

T Cells ◽

Single Cell ◽

Immune Cells ◽

Immune Cell ◽

Cell Types ◽

Effector Memory ◽

Immune Cell Population ◽

Fine Grained ◽

Knowledge Based ◽

Comparable Performance

AbstractSingle-cell RNA sequencing is an emerging strategy for characterizing the immune cell population in diverse environments including blood, tumor or healthy tissues. While this has traditionally been done with flow or mass cytometry targeting protein expression, scRNA-Seq has several established and potential advantages in that it can profile immune cells and non-immune cells (e.g. cancer cells) in the same sample, identify cell types that lack precise markers for flow cytometry, or identify a potentially larger number of immune cell types and activation states than is achievable in a single flow assay. However, scRNA-Seq is currently limited due to the need to identify the types of each immune cell from its transcriptional profile, which is not only time-consuming but also requires a significant knowledge of immunology. While recently developed algorithms accurately annotate coarse cell types (e.g. T cells vs macrophages), making fine distinctions has turned out to be a difficult challenge. To address this, we developed a machine learning classifier called ImmClassifier that leverages a hierarchical ontology of cell type. We demonstrate that ImmClassifier outperforms other tools (+20% recall, +14% precision) in distinguishing fine-grained cell types (e.g. CD8+ effector memory T cells) with comparable performance on coarse ones. Thus, ImmClassifier can be used to explore more deeply the heterogeneity of the immune system in scRNA-Seq experiments.

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P042 CHARACTERIZATION OF INNATE AND ADAPTIVE IMMUNE CELLS INVOLVED IN THE FOREIGN BODY REACTION TO POLYPROPYLENE MESHES IN THE HUMAN ABDOMEN

British Journal of Surgery ◽

10.1093/bjs/znab395.039 ◽

2021 ◽

Vol 108 (Supplement_8) ◽

Author(s):

Axel Dievernich ◽

Pascal Achenbach ◽

Luke Davies ◽

Uwe Klinge

Keyword(s):

T Cells ◽

Foreign Body ◽

Immune Cells ◽

Foreign Body Reaction ◽

Immune Cell ◽

Cell Types ◽

Specific Cell ◽

T Helper ◽

Adaptive Immune ◽

Adaptive Immune Cells

Abstract Aim Polypropylene (PP) mesh is widely used to reinforce tissues. The foreign body reaction (FBR) to the implant is dominated by innate immune cells, especially macrophages. However, considerable numbers of adaptive immune cells have also been regularly observed, which appear to play a crucial role in the long-term host response. This study investigated the FBR to seven human PP meshes, which were removed from the abdomen for recurrence after a median of one year. Material and Methods Using immunofluorescence microscopy and distance maps, the FBR was spatially analyzed for various innate (e.g., CD68+ macrophages, CD56+ NK) and adaptive immune cells (CD3+ T, CD4+ T-helper, CD8+ cytotoxic, FoxP3+ T-regulatory, CD20+ B) as well as “conventional” immune cells (defined as cells expressing their specific immune cell marker without co-expressing CD68). Results T-helper cells (19%) and regulatory T-cells (25%) were present at comparable rates to macrophages, and clustered significantly toward the mesh fibers. For all cell types the lowest proportions of “conventional” cells (< 60%) were observed at the mesh–tissue interface, but increased considerably at about 50–100 µm, indicating reduced stimulation with rising distance to the mesh fibers. Conclusions Both innate and adaptive immune cells participate in the chronic FBR to PP meshes with T cells and macrophages being the predominant cell types, respectively. Furthermore, many cells present a “hybrid” pattern near the mesh fibers. The complexity of the local immune reaction may explain why approaches focusing on specific cell types have not been very successful in reducing the chronic FBR.

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Characterization of innate and adaptive immune cells involved in the foreign body reaction to polypropylene meshes in the human abdomen

Hernia ◽

10.1007/s10029-021-02396-7 ◽

2021 ◽

Author(s):

A. Dievernich ◽

P. Achenbach ◽

L. Davies ◽

U. Klinge

Keyword(s):

T Cells ◽

Foreign Body ◽

Immune Cells ◽

Foreign Body Reaction ◽

Immune Cell ◽

Cell Types ◽

Specific Cell ◽

T Helper ◽

Adaptive Immune ◽

Adaptive Immune Cells

Abstract Background Polypropylene (PP) mesh is widely used to reinforce tissues. The foreign body reaction (FBR) to the implant is dominated by innate immune cells, especially macrophages. However, considerable numbers of adaptive immune cells, namely T cells, have also been regularly observed, which appear to play a crucial role in the long-term host response. Methods This study investigated the FBR to seven human PP meshes, which were removed from the abdomen for recurrence after a median of one year. Using immunofluorescence microscopy, the FBR was examined for various innate (CD11b+ myeloid, CD68+ macrophages, CD56+ NK) and adaptive immune cells (CD3+ T, CD4+ T-helper, CD8+ cytotoxic, FoxP3+ T-regulatory, CD20+ B) as well as “conventional” immune cells (defined as cells expressing their specific immune cell marker without co-expressing CD68). Results T-helper cells (19%) and regulatory T-cells (25%) were present at comparable rates to macrophages, and clustered significantly toward the mesh fibers. For all cell types the lowest proportions of “conventional” cells (< 60%) were observed at the mesh–tissue interface, but increased considerably at about 50–100 µm, indicating reduced stimulation with rising distance to the mesh fibers. Conclusion Both innate and adaptive immune cells participate in the chronic FBR to PP meshes with T cells and macrophages being the predominant cell types, respectively. In concordance with the previous data, many cells presented a “hybrid” pattern near the mesh fibers. The complexity of the immune reaction seen within the foreign body granuloma may explain why approaches focusing on specific cell types have not been very successful in reducing the chronic FBR.

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The roles of immune cells in atherosclerotic calcification

Vascular ◽

10.1177/17085381211032756 ◽

2021 ◽

pp. 170853812110327

Author(s):

Jingsong Cao ◽

Xuyu Zu ◽

Jianghua Liu

Keyword(s):

B Cells ◽

Immune Cells ◽

Cardiovascular Events ◽

Th2 Cells ◽

Regulatory B Cells ◽

T Helper ◽

Relationship Of ◽

The Relationship ◽

Helper Type

Atherosclerosis is the leading cause of acute cardiovascular events, and vascular calcification is an important pathological phenomenon in atherosclerosis. Recently, many studies have shown that immune cells are closely associated with the development of atherosclerosis and calcification, but there are many conflicting viewpoints because of immune system complications, such as the pro-atherosclerotic and atheroprotective effects of regulatory B cells (Bregs), T helper type 2 (Th2) cells and T helper type 17 (Th17) cells. In this review, we summarize the studies on the roles of immune cells, especially lymphocytes and macrophages, in atherosclerotic calcification. Furthermore, we prepared graphs showing the relationship between T cells, B cells and macrophages and atherosclerotic calcification. Finally, we highlight some potential issues that are closely associated with the function of immune cells in atherosclerotic calcification. Based on current research results, this review summarizes the relationship between immune cells and atherosclerotic calcification, and it will be beneficial to understand the relationship of immune cells and atherosclerotic calcification.

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Immune cell composition in normal human kidneys

Scientific Reports ◽

10.1038/s41598-020-72821-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jun-Gyu Park ◽

Myeongsu Na ◽

Min-Gang Kim ◽

Su Hwan Park ◽

Hack June Lee ◽

...

Keyword(s):

T Cells ◽

Immune Cells ◽

Immune Cell ◽

Kidney Diseases ◽

Myeloid Cells ◽

Human Kidney ◽

Effector Memory ◽

Immune Cell Subsets ◽

Immunological Mechanisms ◽

Normal Human

Abstract An understanding of immunological mechanisms in kidney diseases has advanced using mouse kidneys. However, the profiling of immune cell subsets in human kidneys remains undetermined, particularly compared with mouse kidneys. Normal human kidneys were obtained from radically nephrectomised patients with urogenital malignancy (n = 15). Subsequently, human kidney immune cell subsets were analysed using multicolor flow cytometry and compared with subsets from C57BL/6 or BALB/c mice under specific pathogen-free conditions. Twenty kidney sections from healthy kidney donors or subjects without specific renal lesions were additionally analysed by immunohistochemistry. In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3+ T cells. Kidney CD4+ and CD8+ T cells comprised 44% and 56% of total T cells. Of these, 47% ± 15% of T cells displayed an effector memory phenotype (CCR7− CD45RA− CD69−), and 48% ± 19% were kidney-resident cells (CCR7− CD45RA− CD69+). However, the proportions of human CD14+ and CD16+ myeloid cells were approximately 10% of total immune cells. A predominance of CD3+ T cells and a low proportion of CD14+ or CD68+ myeloid cells were also identified in healthy human kidney sections. In mouse kidneys, kidney-resident macrophages (CD11blow F4/80high) were the most predominant subset (up to 50%) but the proportion of CD3+ T cells was less than 20%. These results will be of use in studies in which mouse results are translated into human cases under homeostatic conditions or with disease.

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A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.

Journal of Experimental Medicine ◽

10.1084/jem.183.6.2669 ◽

1996 ◽

Vol 183 (6) ◽

pp. 2669-2674 ◽

Cited By ~ 654

Author(s):

F Powrie ◽

J Carlino ◽

M W Leach ◽

S Mauze ◽

R L Coffman

Keyword(s):

T Cells ◽

Growth Factor ◽

Cd4 T Cells ◽

Transforming Growth Factor ◽

Th2 Cells ◽

Tgf Beta ◽

T Helper ◽

Cd4 Cells ◽

Helper Type

A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed in severe combined immunodeficiency mice reconstituted with CD45RB(high) CD4+ splenic T cells and could be prevented by cotransfer of CD45RB(low) CD4+ T cells. Inhibition of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either the differentiation of function of protective cells as CD45RB(low) CD4+ cells from IL-4-deficient mice were fully effective. These results identify a subpopulation of peripheral CD4+ cells and TGF-beta as critical components of the natural immune regulatory mechanism, which prevents the development of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.

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Authentic Patient-Derived Hepatitis C Virus Infects and Productively Replicates in Primary CD4+and CD8+T LymphocytesIn Vitro

Journal of Virology ◽

10.1128/jvi.01790-17 ◽

2017 ◽

Vol 92 (3) ◽

Cited By ~ 4

Author(s):

Georgia Skardasi ◽

Annie Y. Chen ◽

Tomasz I. Michalak

Keyword(s):

T Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

T Lymphocytes ◽

Immune Cells ◽

Immune Cell ◽

Cell Types ◽

Hcv Rna ◽

Biophysical Properties

ABSTRACTAccumulated evidence indicates that immune cells can support the replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembly. We investigated the ability of authentic, patient-derived HCV to infectin vitrotwo closely related but functionally distinct immune cell types, CD4+and CD8+T lymphocytes, and assessed the properties of the virus produced by these cells. The HCV replication system in intermittently mitogen-stimulated T cells was adapted to infect primary human CD4+or CD8+T lymphocytes. HCV replicated in both cell types although at significantly higher levels in CD4+than in CD8+T cells. Thus, the HCV RNA replicative (negative) strand was detected in CD4+and CD8+cells at estimated mean levels ± standard errors of the means of 6.7 × 102± 3.8 × 102and 1.2 × 102± 0.8 × 102copies/μg RNA, respectively (P< 0.0001). Intracellular HCV NS5a and/or core proteins were identified in 0.9% of CD4+and in 1.2% of CD8+T cells. Double staining for NS5a and T cell type-specific markers confirmed that transcriptionally competent virus replicated in both cell types. Furthermore, an HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4+and CD8+cells. The emergence of unique HCV variants and the release of HCV RNA-reactive particles with biophysical properties different from those of virions in plasma inocula suggested that distinct viral particles were assembled, and therefore, they may contribute to the pool of circulating virus in infected patients.IMPORTANCEAlthough the liver is the main site of HCV replication, infection of the immune system is an intrinsic characteristic of this virus independent of whether infection is symptomatic or clinically silent. Many fundamental aspects of HCV lymphotropism remain uncertain, including the degree to which different immune cells support infection and contribute to virus diversity. We show that authentic, patient-derived HCV productively replicatesin vitroin two closely related but functionally distinct types of T lymphocytes, CD4+and CD8+cells. The display of viral proteins and unique variants, the production of virions with biophysical properties distinct from those in plasma serving as inocula, and inhibition of replication by an antiviral agent led us to ascertain that both T cell subtypes supported virus propagation. Infection of CD4+and CD8+T cells, which are central to adaptive antiviral immune responses, can directly affect HCV clearance, favor virus persistence, and decisively influence the development and progression of hepatitis C.

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Single-Cell Profiling of Kidney Transplant Recipients With Immunosuppressive Treatment Reveals the Dynamic Immune Characteristics

Frontiers in Immunology ◽

10.3389/fimmu.2021.639942 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yongguang Liu ◽

Xiaoyou Liu ◽

Song Zhou ◽

Ruiquan Xu ◽

Jianmin Hu ◽

...

Keyword(s):

T Cells ◽

Kidney Transplantation ◽

Cd8 T Cells ◽

Immune Cells ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Immune Cell ◽

Immunosuppressive Agents ◽

Cell Types ◽

Before And After

Kidney transplantation is currently the first choice of treatment for various types of end-stage renal failure, but there are major limitations in the application of immunosuppressive protocols after kidney transplantation. When the dose of immunosuppressant is too low, graft rejection occurs easily, while a dose that is too high can lead to graft loss. Therefore, it is very important to explore the immune status of patients receiving immunosuppressive agents after kidney transplantation. To compare the immune status of the recipient’s whole peripheral blood before and after receipt of immunosuppressive agents, we used single-cell cytometry by time-of-flight (CyTOF) to detect the peripheral blood immune cells in five kidney transplant recipients (KTRs) from the Department of Organ Transplantation of Zhujiang Hospital of Southern Medical University before and after receiving immunosuppressive agents. Based on CyTOF analysis, we detected 363,342 live single immune cells. We found that the immune cell types of the KTRs before and after receipt of immunosuppressive agents were mainly divided into CD4+ T cells, CD8+ T cells, B cells, NK cells/γδ T cells, monocytes/macrophages, granulocytes, and dendritic cells (DCs). After further reclustering of the above cell types, it was found that the immune cell subclusters in the peripheral blood of patients underwent major changes after receipt of immunosuppressants. After receiving immunosuppressive therapy, the peripheral blood of KTRs had significantly increased levels of CD57+NK cells and significantly decreased levels of central memory CD4+ T cells, follicular helper CD4+ T cells, effector CD8+ T cells, effector memory CD8+ T cells and naive CD8+ T cells. This study used CyTOF to classify immune cells in the peripheral blood of KTRs before and after immunosuppressive treatment, further compared differences in the proportions of the main immune cell types and immune cell subgroups before and after receipt of immunosuppressants, and provided relatively accurate information for assessment and treatment strategies for KTRs.

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T helper cells modulate intestinal stem cell renewal and differentiation

10.1101/217133 ◽

2017 ◽

Cited By ~ 2

Author(s):

Moshe Biton ◽

Adam L. Haber ◽

Semir Beyaz ◽

Noga Rogel ◽

Christopher Smillie ◽

...

Keyword(s):

Stem Cells ◽

T Cells ◽

Epithelial Cells ◽

Immune Cell ◽

Intestinal Epithelial Cells ◽

Cell Types ◽

Intestinal Epithelial ◽

T Helper ◽

Self Renewal

AbstractIn the small intestine, a cellular niche of diverse accessory cell types supports the rapid generation of mature epithelial cell types through self-renewal, proliferation, and differentiation of intestinal stem cells (ISCs). However, not much is known about interactions between immune cells and ISCs, and it is unclear if and how immune cell dynamics affect eventual ISC fate or the balance between self-renewal and differentiation. Here, we used single-cell RNA-seq (scRNA-Seq) of intestinal epithelial cells (IECs) to identify new mechanisms for ISC–immune cell interactions. Surprisingly, MHC class II (MHCII) is enriched in two distinct subsets of Lgr5+ crypt base columnar ISCs, which are also distinguished by higher proliferation rates. Using co-culture of T cells with intestinal organoids, cytokine stimulations, and in vivo mouse models, we confirm that CD4+ T helper (Th) cells communicate with ISCs and affect their differentiation, in a manner specific to the Th subtypes and their signature cytokines and dependent on MHCII expression by ISCs. Specific inducible knockout of MHCII in intestinal epithelial cells in mice in vivo results in expansion of the ISC pool. Mice lacking T cells have expanded ISC pools, whereas specific depletion of Treg cells in vivo results in substantial reduction of ISC numbers. Our findings show that interactions between Th cells and ISCs mediated via MHCII expressed in intestinal epithelial stem cells help orchestrate tissue-wide responses to external signals.

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Impaired development of human Th1 cells in patients with deficient expression of STAT4

Blood ◽

10.1182/blood-2008-09-179820 ◽

2009 ◽

Vol 113 (23) ◽

pp. 5887-5890 ◽

Cited By ~ 29

Author(s):

Hua-Chen Chang ◽

Ling Han ◽

Ritobrata Goswami ◽

Evelyn T. Nguyen ◽

David Pelloso ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Ectopic Expression ◽

Th2 Cells ◽

Th1 Cells ◽

Type I ◽

T Helper ◽

Helper Type

Abstract IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ, IL-12Rβ2, and TNFα is greatly reduced in Th1 cultures of CD4 T cells isolated from lymphoma patients after autologous stem cell transplantation who have acquired STAT4 deficiency. Moreover, IL-4 and IL-5 production is increased in patient Th1 cultures though there are no defects in the development of Th2 cells. Reconstitution of STAT4 in patient T cells allowed recovery of IFNγ and IL-12Rβ2 expression, whereas ectopic expression of IL-12Rβ2 did not rescue STAT4 expression, and increased IFNγ production only to levels intermediate between control and patient samples. These results demonstrate that, as in murine systems, STAT4 is required for optimal human Th1 lineage development.

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