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Cytometry. Part a : the Journal of the... Mar 2021Determining the abundance of leukocyte subtypes, including lymphocyte subpopulations, not only in blood but also in lymphatic tissues, is inevitable to assess the immune...
Determining the abundance of leukocyte subtypes, including lymphocyte subpopulations, not only in blood but also in lymphatic tissues, is inevitable to assess the immune status of an organism for research purposes. However, nucleated thrombocytes and erythrocytes exacerbate many hematological techniques in avian species. In order to enable a rapid discrimination of leukocyte subsets from lymphatic tissues of chicken, we adapted existing flow cytometric methods for counting leukocytes in chicken blood. We established staining and gating strategies allowing the flow cytometric characterization and enumeration of total leukocytes, thrombocytes, monocytes/macrophages, CD8α lymphocytes, CD4 T cells, γδ T cells, and B cells in chicken spleen and CD8α lymphocytes, CD4 T cells, γδ T cells, and B cells among intraepithelial lymphocytes in chicken cecal tonsils. For this, we prepared single-cell suspensions of spleen and isolated intraepithelial lymphocytes from cecal tonsils without density centrifugation, and performed antibody staining of cells without subsequent washing steps to prevent cell loss and falsification of obtained cell counts. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.
Topics: Animals; B-Lymphocytes; Chickens; Flow Cytometry; Leukocytes; Lymphoid Tissue; T-Lymphocyte Subsets
PubMed: 32833295
DOI: 10.1002/cyto.a.24214 -
Annual Review of Immunology 2008Secondary lymphoid organs develop during embryogenesis or in the first few weeks after birth according to a highly coordinated series of interactions between newly... (Review)
Review
Secondary lymphoid organs develop during embryogenesis or in the first few weeks after birth according to a highly coordinated series of interactions between newly emerging hematopoietic cells and immature mesenchymal or stromal cells. These interactions are orchestrated by homeostatic chemokines, cytokines, and growth factors that attract hematopoietic cells to sites of future lymphoid organ development and promote their survival and differentiation. In turn, lymphotoxin-expressing hematopoietic cells trigger the differentiation of stromal and endothelial cells that make up the scaffolding of secondary lymphoid organs. Lymphotoxin signaling also maintains the expression of adhesion molecules and chemokines that govern the ultimate structure and function of secondary lymphoid organs. Here we describe the current paradigm of secondary lymphoid organ development and discuss the subtle differences in the timing, molecular interactions, and cell types involved in the development of each secondary lymphoid organ.
Topics: Animals; Cytokines; Lymph Nodes; Lymphoid Tissue; Mice; Nasal Mucosa; Peyer's Patches; Signal Transduction
PubMed: 18370924
DOI: 10.1146/annurev.immunol.26.021607.090257 -
Frontiers in Immunology 2018Tissue-resident memory T cells (T cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood.... (Review)
Review
Tissue-resident memory T cells (T cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8 T cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4 T cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of T populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8 T cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of T cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all T persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8 T cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8 T cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of T cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that maintain T cells in different tissues.
Topics: Animals; Biomarkers; Cellular Microenvironment; Humans; Immunity, Cellular; Immunologic Memory; Lymphoid Tissue; Organ Specificity; T-Lymphocytes
PubMed: 29904388
DOI: 10.3389/fimmu.2018.01214 -
Advances in Cancer Research 2015The inflammatory status of the tumor microenvironment (TME) has been heavily investigated in recent years. Chemokine- and cytokine-signaling pathways such as CCR7,... (Review)
Review
The inflammatory status of the tumor microenvironment (TME) has been heavily investigated in recent years. Chemokine- and cytokine-signaling pathways such as CCR7, CXCR5, lymphotoxin, and IL-36, which are involved in the generation of secondary lymphoid organs and effector immune responses, are now recognized as having value both as prognostic factors and as immunomodulatory therapeutics in the context of cancer. Furthermore, when produced in the TME, these mediators have been shown to promote the recruitment of immune cells, including T cells, B cells, dendritic cells (DCs), and other specialized immune cell subsets such as follicular DCs and T follicular helper cells, in association with the formation of "tertiary" lymphoid structures (TLSs) within or adjacent to sites of disease. Although TLSs are composed of a heterogeneous collection of immune cell types, whose composition differs based on cancer subtype, the qualitative presence of TLSs has been shown to represent a biomarker of good prognosis for cancer patients. A comprehensive understanding of the role each of these pathways plays within the TME may support the rational design of future immunotherapies to selectively promote/bolster TLS formation and function, leading to improved clinical outcomes across the vast range of solid cancer types.
Topics: Animals; Humans; Lymphoid Tissue; Neoplasms; Organogenesis; Tumor Microenvironment
PubMed: 26216634
DOI: 10.1016/bs.acr.2015.04.003 -
Stem Cell Reports Jun 2019Lymph nodes (LNs) are secondary lymphoid tissues that play a critical role in filtering the lymph and promoting adaptive immune responses. Surgical resection of LNs,...
Lymph nodes (LNs) are secondary lymphoid tissues that play a critical role in filtering the lymph and promoting adaptive immune responses. Surgical resection of LNs, radiation therapy, or infections may damage lymphatic vasculature and compromise immune functions. Here, we describe the generation of functional synthetic lympho-organoids (LOs) using LN stromal progenitors and decellularized extracellular matrix-based scaffolds, two basic constituents of secondary lymphoid tissues. We show that upon transplantation at the site of resected LNs, LOs become integrated into the endogenous lymphatic vasculature and efficiently restore lymphatic drainage and perfusion. Upon immunization, LOs support the activation of antigen-specific immune responses, thus acquiring properties of native lymphoid tissues. These findings provide a proof-of-concept strategy for the development of functional lympho-organoids suitable for restoring lymphatic and immune cell functions.
Topics: Animals; Cells, Immobilized; Extracellular Matrix; Lymph Nodes; Mice; Mice, Transgenic; Organoids; Regeneration; Tissue Scaffolds
PubMed: 31155505
DOI: 10.1016/j.stemcr.2019.04.021 -
Scientific Reports Jan 2017Development of lymphoid tissue is determined by interactions between stromal lymphoid tissue organiser (LTo) and hematopoietic lymphoid tissue inducer (LTi) cells. A...
Development of lymphoid tissue is determined by interactions between stromal lymphoid tissue organiser (LTo) and hematopoietic lymphoid tissue inducer (LTi) cells. A failure for LTo to receive appropriate activating signals during embryogenesis through lymphotoxin engagement leads to a complete cessation of lymph node (LN) and Peyer's patch development, identifying LTo as a key stromal population for lymphoid tissue organogenesis. However, little is known about the equivalent stromal cells that induce spleen development. Here, by dissociating neonatal murine spleen stromal tissue for re-aggregation and transplant into adult mouse recipients, we have identified a MAdCAM-1CD31CD201 spleen stromal organizer cell-type critical for new tissue formation. This finding provides an insight into the regulation of post-natal spleen tissue organogenesis, and could be exploited in the development of spleen regenerative therapies.
Topics: Animals; Animals, Newborn; Antigens, CD; Biomarkers; Cell Aggregation; Gene Expression Regulation; Lymphoid Tissue; Magnetics; Mesoderm; Mice; Mice, Inbred BALB C; RNA, Messenger; Regeneration; Spleen; Stromal Cells
PubMed: 28067323
DOI: 10.1038/srep40401 -
Discovery Medicine Oct 2011The generation of functional artificial lymphoid tissue will be a major focus of future research. In humans, this will be an alternative tool which induces specific... (Review)
Review
The generation of functional artificial lymphoid tissue will be a major focus of future research. In humans, this will be an alternative tool which induces specific immune responses at ectopic sites and offers a novel way to restore the immune status and to treat uncontrollable obstinate diseases such as cancer, autoimmune diseases, severe infection, and immunodeficiency caused by primary defect or aging. Artificially synthesized lymphoid tissue may also provide us with a highly informative method to further study development and physiological functions of lymphoid tissues and organs. We recently reported successful generation of artificial lymph node-like tissues at ectopic sites in mouse. They showed a remarkable ability to induce secondary immune responses upon antigen stimulation, especially when transplanted into naïve or immunodeficient hosts. In this review, before discussing generation of synthetic immune systems, we first summarize previous knowledge on lymphoid development, which provides information valuable for making artificial lymphoid tissues such as spleen and lymph nodes. Then, we discuss problems that need to be solved in order to synthesize artificial lymphoid tissues, including several issues such as combinations of stromal cells, their cell types, soluble factors, and scaffold properties that enable proper accumulation and organization of immune cells in grafts.
Topics: Adaptive Immunity; Animals; Artificial Organs; Humans; Lymphoid Tissue; Mice
PubMed: 22031672
DOI: No ID Found -
Scientific Reports Nov 2022Histological sections of the lymphatic system are usually the basis of static (2D) morphological investigations. Here, we performed a dynamic (4D) analysis of human...
Histological sections of the lymphatic system are usually the basis of static (2D) morphological investigations. Here, we performed a dynamic (4D) analysis of human reactive lymphoid tissue using confocal fluorescent laser microscopy in combination with machine learning. Based on tracks for T-cells (CD3), B-cells (CD20), follicular T-helper cells (PD1) and optical flow of follicular dendritic cells (CD35), we put forward the first quantitative analysis of movement-related and morphological parameters within human lymphoid tissue. We identified correlations of follicular dendritic cell movement and the behavior of lymphocytes in the microenvironment. In addition, we investigated the value of movement and/or morphological parameters for a precise definition of cell types (CD clusters). CD-clusters could be determined based on movement and/or morphology. Differentiating between CD3- and CD20 positive cells is most challenging and long term-movement characteristics are indispensable. We propose morphological and movement-related prototypes of cell entities applying machine learning models. Finally, we define beyond CD clusters new subgroups within lymphocyte entities based on long term movement characteristics. In conclusion, we showed that the combination of 4D imaging and machine learning is able to define characteristics of lymphocytes not visible in 2D histology.
Topics: Humans; Lymphoid Tissue; Dendritic Cells, Follicular; T-Lymphocytes, Helper-Inducer; Lymphocytes; Machine Learning
PubMed: 36347879
DOI: 10.1038/s41598-022-18097-9 -
Cellular & Molecular Immunology Sep 2012
Topics: Animals; Autoimmunity; Homeostasis; Humans; Hypersensitivity; Lymphoid Tissue; Receptors, Cytokine; T-Lymphocytes, Helper-Inducer
PubMed: 22941434
DOI: 10.1038/cmi.2012.27 -
Microscopy and Microanalysis : the... Aug 2012The immune system is highly evolved and can respond to infection throughout the body. Pathogenspecific immune cells are usually generated in secondary lymphoid tissues... (Review)
Review
The immune system is highly evolved and can respond to infection throughout the body. Pathogenspecific immune cells are usually generated in secondary lymphoid tissues (e.g., spleen, lymph nodes) and then migrate to sites of infection where their functionality is shaped by the local milieu. Because immune cells are so heavily influenced by the infected tissue in which they reside, it is important that their interactions and dynamics be studied in vivo. Two-photon microscopy is a powerful approach to study host-immune interactions in living tissues, and recent technical advances in the field have enabled researchers to capture movies of immune cells and infectious agents operating in real time. These studies have shed light on pathogen entry and spread through intact tissues as well as the mechanisms by which innate and adaptive immune cells participate in thwarting infections. This review focuses on how two-photon microscopy can be used to study tissue-specific immune responses in vivo, and how this approach has advanced our understanding of host-immune interactions following infection.
Topics: Animals; Diagnostic Imaging; Host-Pathogen Interactions; Humans; Immune System; Infections; Lymphoid Tissue; Microscopy
PubMed: 22846498
DOI: 10.1017/S1431927612000281