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Cold Spring Harbor Perspectives in... Oct 2021Immunological memory and exhaustion are fundamental features of adaptive immunity. Recent advances reveal increasing heterogeneity and diversity among CD8 T-cell... (Review)
Review
Immunological memory and exhaustion are fundamental features of adaptive immunity. Recent advances reveal increasing heterogeneity and diversity among CD8 T-cell subsets, resulting in new subsets to annotate and understand. Here, we review our current knowledge of differentiation and maintenance of memory and exhausted CD8 T cells, including phenotypic classification, developmental paths, transcriptional and epigenetic features, and cell intrinsic and extrinsic factors. Additionally, we use this outline to discuss the nomenclature of effector, memory, and exhausted CD8 T cells. Finally, we discuss how new findings about these cell types may impact the therapeutic efficacy and development of immunotherapies targeting effector, memory, and/or exhausted CD8 T cells in chronic infections and cancer.
Topics: Animals; Cell Differentiation; Epigenesis, Genetic; Humans; Immunologic Memory; T-Lymphocyte Subsets; Terminology as Topic
PubMed: 33782027
DOI: 10.1101/cshperspect.a037929 -
Science (New York, N.Y.) Apr 2016The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity, as well as in mammals,... (Review)
Review
The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity, as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed "trained immunity" or "innate immune memory." Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, new therapeutic strategies for the treatment of immune deficiency states, and modulation of exaggerated inflammation in autoinflammatory diseases.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Immunity, Innate; Immunologic Memory; Infections; Inflammation; Invertebrates; Plants; Transcription, Genetic; Vaccination; Vaccines
PubMed: 27102489
DOI: 10.1126/science.aaf1098 -
Nature Reviews. Immunology Jun 2020Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent... (Review)
Review
Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
Topics: Adaptive Immunity; Animals; Epigenesis, Genetic; Humans; Immune System; Immune System Diseases; Immune Tolerance; Immunity, Innate; Immunologic Memory; Inflammation
PubMed: 32132681
DOI: 10.1038/s41577-020-0285-6 -
Nature Immunology Jun 2023Specialized subpopulations of CD4 T cells survey major histocompatibility complex class II-peptide complexes to control phagosomal infections, help B cells, regulate... (Review)
Review
Specialized subpopulations of CD4 T cells survey major histocompatibility complex class II-peptide complexes to control phagosomal infections, help B cells, regulate tissue homeostasis and repair or perform immune regulation. Memory CD4 T cells are positioned throughout the body and not only protect the tissues from reinfection and cancer, but also participate in allergy, autoimmunity, graft rejection and chronic inflammation. Here we provide updates on our understanding of the longevity, functional heterogeneity, differentiation, plasticity, migration and human immunodeficiency virus reservoirs as well as key technological advances that are facilitating the characterization of memory CD4 T cell biology.
Topics: Humans; CD4-Positive T-Lymphocytes; Memory T Cells; Immunologic Memory
PubMed: 37156885
DOI: 10.1038/s41590-023-01510-4 -
Cell Host & Microbe Jan 2019Immunological memory is an important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and... (Review)
Review
Immunological memory is an important evolutionary trait that improves host survival upon reinfection. Memory is a characteristic recognized within both the innate and adaptive arms of the immune system. Although the mechanisms and properties through which innate and adaptive immune memory are induced are distinct, they collude to improve host defense to pathogens. Here, we propose that innate immune memory, or "trained immunity," is a primitive form of adaptation in host defense, resulting from chromatin structure rearrangement, which provides an increased but non-specific response to reinfection. In contrast, adaptive immune memory is more advanced, with increased magnitude of response mediated through epigenetic changes, as well as specificity mediated by gene recombination. An integrative model of immune memory is important for broad understanding of host defense, and for identifying the most effective approaches to modulate it for the benefit of patients with infections and immune-mediated diseases.
Topics: Adaptive Immunity; Animals; Biological Evolution; Epigenesis, Genetic; Humans; Immunity, Innate; Immunologic Memory; Infections; Lymphocytes; Recombination, Genetic
PubMed: 30629914
DOI: 10.1016/j.chom.2018.12.006 -
Frontiers in Immunology 2018CD8 T cells comprising the memory pool display considerable heterogeneity, with individual cells differing in phenotype and function. This review will focus on our... (Review)
Review
CD8 T cells comprising the memory pool display considerable heterogeneity, with individual cells differing in phenotype and function. This review will focus on our current understanding of heterogeneity within the antigen-specific memory CD8 T cell compartment and classifications of memory CD8 T cell subsets with defined and discrete functionalities. Recent data suggest that phenotype and/or function of numerically stable circulatory memory CD8 T cells are defined by the age of memory CD8 T cell (or time after initial antigen-encounter). In addition, history of antigen stimulations has a profound effect on memory CD8 T cell populations, suggesting that repeated infections (or vaccination) have the capacity to further shape the memory CD8 T cell pool. Finally, genetic background of hosts and history of exposure to diverse microorganisms likely contribute to the observed heterogeneity in the memory CD8 T cell compartment. Extending our tool box and exploring alternative mouse models (i.e., "dirty" and/or outbred mice) to encompass and better model diversity observed in humans will remain an important goal for the near future that will likely shed new light into the mechanisms that govern biology of memory CD8 T cells.
Topics: Aging; Animals; CD8-Positive T-Lymphocytes; Humans; Immunologic Memory; Mice; Models, Immunological
PubMed: 30515169
DOI: 10.3389/fimmu.2018.02692 -
Cells Feb 2020CD4 T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and... (Review)
Review
CD4 T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4 T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4 tissue-resident memory T cells and of CD4 memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4 T cell-mediated autoimmune diseases.
Topics: Autoimmune Diseases; CD4-Positive T-Lymphocytes; Cell Differentiation; Humans; Immunologic Memory
PubMed: 32106536
DOI: 10.3390/cells9030531 -
Nature Reviews. Immunology Apr 2020Surviving a single infection often results in lifelong immunity to the infecting pathogen. Such protection is mediated, in large part, by two main B cell memory 'walls'... (Review)
Review
Surviving a single infection often results in lifelong immunity to the infecting pathogen. Such protection is mediated, in large part, by two main B cell memory 'walls' - namely, long-lived plasma cells and memory B cells. The cellular and molecular processes that drive the production of long-lived plasma cells and memory B cells are subjects of intensive research and have important implications for global health. Indeed, although nearly all vaccines in use today depend on their ability to induce B cell memory, we have not yet succeeded in developing vaccines for some of the world's most deadly diseases, including AIDS and malaria. Here, we describe the two-phase process by which antigen drives the generation of long-lived plasma cells and memory B cells and highlight the challenges for successful vaccine development in each phase.
Topics: Antigens; B-Lymphocytes; Communicable Diseases; Humans; Immunologic Memory; Plasma Cells; Vaccines
PubMed: 31836872
DOI: 10.1038/s41577-019-0244-2 -
Physiological Reviews Jan 2023The mechanisms underlying innate immune memory have been extensively explored in the last decades but are in fact largely unknown. Although the specificity of adaptive... (Review)
Review
The mechanisms underlying innate immune memory have been extensively explored in the last decades but are in fact largely unknown. Although the specificity of adaptive immune memory in vertebrates is ensured through the recombination of immunoglobulin family genes and clonal expansion, the basic mechanisms of innate immune cells' nonspecific increased responsiveness rely on epigenetic, transcriptional, and metabolic programs after transient stimulation. Changes in these programs result in enhanced responsiveness to secondary challenges with a wide variety of stimuli. This phenomenon is termed "trained immunity" or "innate immune memory." On one hand, trained immunity improves the response to infections and vaccination, facilitating stronger innate immune responses and enhanced protection against a variety of microbial stimuli. Conversely, trained immunity may contribute to the pathophysiology of cardiovascular, autoinflammatory, and neurodegenerative diseases. In this review, we gather the current body of knowledge in this field and summarize the foundations and mechanisms of trained immunity, the different cell types involved, its consequences for health and disease, and the potential of its modulation as a therapeutic tool.
Topics: Adaptive Immunity; Animals; Humans; Immunity, Innate; Immunoglobulins; Immunologic Memory
PubMed: 35981301
DOI: 10.1152/physrev.00031.2021 -
Nature Reviews. Immunology Nov 2012During an infection, T cells can differentiate into multiple types of effector and memory T cells, which help to mediate pathogen clearance and provide long-term... (Review)
Review
During an infection, T cells can differentiate into multiple types of effector and memory T cells, which help to mediate pathogen clearance and provide long-term protective immunity. These cells can vary in their phenotype, function and location, and in their long-term fate in terms of their ability to populate the memory T cell pool. Over the past decade, the signalling pathways and transcriptional programmes that regulate the formation of heterogeneous populations of effector and memory CD8(+) T cells have started to be characterized, and this Review discusses the major advances in these areas.
Topics: Animals; CD8-Positive T-Lymphocytes; Cell Differentiation; Gene Expression Regulation; Humans; Immunologic Memory; Infections; Lymphocyte Activation; Signal Transduction; Transcription, Genetic
PubMed: 23080391
DOI: 10.1038/nri3307