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Exercise Immunology Review 2016Human cytomegalovirus (HCMV) is a ubiquitous -herpes virus that has co-evolved with its host since the very beginning of human life. The vast majority of adults... (Review)
Review
Human cytomegalovirus (HCMV) is a ubiquitous -herpes virus that has co-evolved with its host since the very beginning of human life. The vast majority of adults worldwide carry the virus in a latent state, which is known to have striking effects on the composition and function of both T-cells and NK-cells. While there is evidence to suggest that prior exposure to HCMV can have beneficial effects in the immune competent host, poor control of the virus may contribute to T-cell exhaustion and the early onset of immunosenescence. The interaction between HCMV and exercise has garnered a lot of recent research attention. This stemmed from observations that people with HCMV redeploy greater numbers of CD8+ T-cells in response to a single exercise bout, while NK-cell mobilization is, conversely, impaired. Moreover, athletes with latent HCMV infection may be better protected against symptoms of upper respiratory illness (URI), and it has been suggested that the host's ability to control HCMV (i.e. keeping CMV in a latent state) may connect apparent bidirectional effects of exercise volume on host immunity and infection risk. This work has set a new paradigm that immune responses to both acute and chronic exercise might be governed by the infection history of the host. In this review, we summarize current knowledge on the effects of HCMV infection on T-cells and NK-cells and synthesize the literature on HCMV and the immune response to both single exercise bouts and prolonged periods of exercise training. We also discuss potential clinical and practical applications of this work including the use of HCMV reactivation as a biomarker of immune depression in athletes, its relevance in immunosenescence and the associated immune risk profile, and the potential for exercise to augment vaccine responses and the man ufacture of immune cells for adoptive transfer immunotherapy. Although research in this area is still in its infancy, we conclude that host infection history and the ability to regulate dormant pathogens is likely to play a key role in our understanding of how the immune system responds to both acute and chronic exercise across the entire exercise volume continuum.
Topics: CD8-Positive T-Lymphocytes; Cytomegalovirus; Cytomegalovirus Infections; Exercise; Humans; Immunotherapy, Adoptive; Killer Cells, Natural
PubMed: 26853134
DOI: No ID Found -
Nature Biomedical Engineering Jan 2021The function of a T cell depends on its subtype and activation state. Here, we show that imaging of the autofluorescence lifetime signals of quiescent and activated T...
The function of a T cell depends on its subtype and activation state. Here, we show that imaging of the autofluorescence lifetime signals of quiescent and activated T cells can be used to classify the cells. T cells isolated from human peripheral blood and activated in culture using tetrameric antibodies against the surface ligands CD2, CD3 and CD28 showed specific activation-state-dependent patterns of autofluorescence lifetime. Logistic regression models and random forest models classified T cells according to activation state with 97-99% accuracy, and according to activation state (quiescent or activated) and subtype (CD3CD8 or CD3CD4) with 97% accuracy. Autofluorescence lifetime imaging can be used to non-destructively determine T-cell function.
Topics: Cells, Cultured; Humans; Lymphocyte Activation; Optical Imaging; T-Lymphocytes
PubMed: 32719514
DOI: 10.1038/s41551-020-0592-z -
Trends in Molecular Medicine Jul 2016Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently,... (Review)
Review
Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we review the link between exercise and NK cell function, focusing on circulating exercise factors and additional effects, including vascularization, hypoxia, and body temperature in mediating the effects on NK cell functionality. Exercise-dependent mobilization and activation of NK cells provides a mechanistic explanation for the protective effect of exercise on cancer, and we propose that exercise represents a potential strategy as adjuvant therapy in cancer, by improving NK cell recruitment and infiltration in solid tumors.
Topics: Animals; Exercise; Exercise Therapy; Humans; Immunity, Cellular; Killer Cells, Natural; Lymphocyte Activation; Neoplasms
PubMed: 27262760
DOI: 10.1016/j.molmed.2016.05.007 -
Immunological Reviews May 2020The complement system represents one of the evolutionary oldest arms of our immune system and is commonly recognized as a liver-derived and serum-active system critical... (Review)
Review
The complement system represents one of the evolutionary oldest arms of our immune system and is commonly recognized as a liver-derived and serum-active system critical for providing protection against invading pathogens. Recent unexpected findings, however, have defined novel and rather "uncommon" locations and activities of complement. Specifically, the discovery of an intracellularly active complement system-the complosome-and its key role in the regulation of cell metabolic pathways that underly normal human T cell responses have taught us that there is still much to be discovered about this system. Here, we summarize the current knowledge about the emerging functions of the complosome in T cell metabolism. We further place complosome activities among the non-canonical roles of other intracellular innate danger sensing systems and argue that a "location-centric" view of complement evolution could logically justify its close connection with the regulation of basic cell physiology.
Topics: Animals; Biomarkers; Complement Activation; Complement System Proteins; Disease Susceptibility; Energy Metabolism; Homeostasis; Humans; Lymphocyte Activation; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 32166778
DOI: 10.1111/imr.12852 -
Frontiers in Immunology 2022Tissue-resident memory T (T) cells have emerged as key players in the immune control of melanoma. These specialized cells are identified by expression of tissue... (Review)
Review
Tissue-resident memory T (T) cells have emerged as key players in the immune control of melanoma. These specialized cells are identified by expression of tissue retention markers such as CD69, CD103 and CD49a with downregulation of egress molecules such as Sphingosine-1-Phosphate Receptor-1 (S1PR1) and the lymphoid homing receptor, CD62L. T have been shown to be integral in controlling infections such as herpes simplex virus (HSV), lymphocytic choriomeningitis virus (LCMV) and influenza. More recently, robust pre-clinical models have also demonstrated T are able to maintain melanoma in a dormant state without progression to macroscopic disease reminiscent of their ability to control viral infections. The discovery of the role these cells play in anti-melanoma immunity has coincided with the advent of immune checkpoint inhibitor (ICI) therapy which has revolutionized the treatment of cancers. ICIs that target programmed death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) have led to substantial improvements in outcomes for patients with metastatic melanoma and have been rapidly employed to reduce recurrences in the resected stage III setting. While ICIs mediate anti-tumor activity CD8 T cells, the specific subsets that facilitate this response is unclear. T invariably exhibit high expression of immune checkpoints such as PD-1, CTLA-4 and lymphocyte activating gene-3 (LAG-3) which strongly implicates this CD8 T cell subset as a crucial mediator of ICI activity. In this review, we present pre-clinical and translational studies that highlight the critical role of T in both immune control of primary melanoma and as a key CD8 T cell subset that mediates anti-tumor activity of ICIs for the treatment of melanoma.
Topics: Humans; CTLA-4 Antigen; Memory T Cells; CD8-Positive T-Lymphocytes; Programmed Cell Death 1 Receptor; Melanoma
PubMed: 36466880
DOI: 10.3389/fimmu.2022.1048758 -
International Immunopharmacology Oct 2015The adaptive immune system, composed of lymphocytes, recognizes diversified antigens and generates immunological memory. According to the canonical model, it is the... (Review)
Review
The adaptive immune system, composed of lymphocytes, recognizes diversified antigens and generates immunological memory. According to the canonical model, it is the innate immune system that captures pathogens and senses environment to activate adaptive lymphocytes through antigen presentation, costimulatory signals and cytokine milieu. Emerging evidence indicates that environmental cues can be directly conveyed to lymphocytes by the aryl hydrocarbon receptor (AhR). AhR is a ligand-activated transcription factor that widely expresses in many immune cell lineages and recognizes a broad range of ligands including endogenous and dietary metabolites, microbial derivatives and xenobiotics. This review will focus on the regulatory role of AhR in not only adaptive but also innate lymphocytes including recently discovered innate lymphoid cells.
Topics: Adaptive Immunity; Animals; Homeostasis; Humans; Immunity, Innate; Lymphocytes; Receptors, Aryl Hydrocarbon
PubMed: 25907242
DOI: 10.1016/j.intimp.2015.03.046 -
Annals of the New York Academy of... Sep 2015Cortistatin is a neuropeptide isolated from cortical brain regions, showing high structural homology and sharing many functions with somatostatin. However, cortistatin... (Review)
Review
Cortistatin is a neuropeptide isolated from cortical brain regions, showing high structural homology and sharing many functions with somatostatin. However, cortistatin exerts unique functions in the central nervous and immune systems, including decreasing locomotor activity, inducing sleep-promoting effects, and deactivating inflammatory and T helper (TH )1/TH 17-driven responses in preclinical models of sepsis, arthritis, multiple sclerosis, and colitis. Besides its release by cortical and hippocampal interneurons, cortistatin is produced by macrophages, lymphocytes, and peripheral nociceptive neurons in response to inflammatory stimuli, supporting a physiological role of cortistatin in the immune and nociceptive systems. Cortistatin-deficient mice have been shown to have exacerbated nociceptive responses to neuropathic and inflammatory pain sensitization. However, a paradoxical effect has been observed in studies of immune disorders, in which, despite showing competent inflammatory/autoreactive responses, cortistatin-deficient mice were partially resistant to systemic autoimmunity and inflammation. This unexpected phenotype was associated with elevated circulating glucocorticoids and anxiety-like behavior. These findings support cortistatin as a novel multimodal therapeutic approach to treat autoimmunity and clinical pain and identify it as a key endogenous component of the neuroimmune system related to stress responses.
Topics: Animals; Anti-Inflammatory Agents; Autoimmune Diseases; Cerebral Cortex; Disease Models, Animal; Humans; Inflammation; Macrophages; Mice; Motor Activity; Neuropeptides; Nociceptors; Sleep; Somatostatin; Th1 Cells; Th17 Cells
PubMed: 25951888
DOI: 10.1111/nyas.12789 -
Advances in Experimental Medicine and... 2017Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also... (Review)
Review
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL). In addition, NK cells express, in a stochastic manner, an array of germ line-encoded activating and inhibitory receptors that recognize the polymorphic regions of major histocompatibility class I (MHC-I) molecules and self-proteins. Recognition of self renders NK cell tolerance to self-healthy tissues, but fail to recognize self ('missing-self') leads to activation to neoplastic transformation and infections of certain viruses. In this chapter, we will summarize the development of NK cells in the context of ILCs, describe the diversity of phenotype and function in blood and tissues, and discuss their involvement in health and diseases in humans.
Topics: Animals; Cell Differentiation; Cytokines; Humans; Killer Cells, Natural; Lymphocyte Subsets; Lymphocytes
PubMed: 28921473
DOI: 10.1007/978-981-10-5987-2_11 -
Journal of Cellular Physiology Nov 2022This perspective review highlights the impact of physical exercise on immunometabolic responses in the past 5 years. Understanding immunometabolism as a part of... (Review)
Review
This perspective review highlights the impact of physical exercise on immunometabolic responses in the past 5 years. Understanding immunometabolism as a part of immunological research is essential. Furthermore, the roles of both acute and chronic effects of physical exercise on health, aging, and chronic diseases in immunometabolic changes should be elaborated. In immune cells, β2 adrenergic signaling stimulates the preferential mobilization of inflammatory phenotypes, such as CD16 monocytes and CD8 T cells, into the bloodstream after a physical exercise session. The mobilization of immune cells is closely related to the availability of energetic substrates for the cell and mechanisms associated with the uptake and oxidation of fatty acids and glucose. These cells, especially senescent T cells, are mobilized to the peripheral tissues and undergo apoptotic signaling, stimulating the creation of a "vacant space" where new cells will be matured and replaced in the circulation. This results in the upregulation of the expression and secretion of anti-inflammatory cytokines (IL-10 and IL-1ra), leading to increased regulatory immune cells that provide immunoregulatory properties. Thus, we suggest that a significant nutrient available to the cell will favor oxidative metabolism, augment ATP production, and consequently maintain the immune cells in their quiescent state, as well as promote rapid activation function. Therefore, based on the studies discussed in this perspective review, we highlight the importance of performing moderate-intensity continuous and high-intensity intermittent aerobic exercises, due to a higher magnitude of energetic demand and release of anti-inflammatory cytokines (IL-6 and IL-10).
Topics: Interleukin-10; CD8-Positive T-Lymphocytes; Exercise; Cytokines; Anti-Inflammatory Agents
PubMed: 36052887
DOI: 10.1002/jcp.30866 -
Autoimmunity Reviews Dec 2015Interleukin-27 (IL-27) is a new member of the IL-12 family. It is produced by activated antigen-presenting cells and plays an important role in the regulation of CD4+ T... (Review)
Review
Interleukin-27 (IL-27) is a new member of the IL-12 family. It is produced by activated antigen-presenting cells and plays an important role in the regulation of CD4+ T cell differentiation and immune response. IL-27 activates multiple signaling cascades, including the JAK-STAT and p38 MAPK pathways. Several studies have revealed that IL-27 promotes the differentiation of Th1 and Tr1, but inhibits Th2, Th17, and Treg cells. However, a few studies have shown an opposite effect on certain T cell subsets, such as Treg. IL-27 displays both pro- and anti- inflammatory activities in different autoimmune diseases. Here, we have discussed the role of IL-27 in rheumatoid arthritis, multiple sclerosis, colitis, lupus, psoriasis, type 1 diabetes, and uveitis. Most of this information is derived from experimental models of these autoimmune diseases. The mechanistic basis of the dual role of IL-27 in inflammation and autoimmunity is still not fully defined. In general, the pro-/anti-inflammatory activity of IL-27 is influenced by the underlying immune effector pathways, the phase of the disease, the presence or absence of counter-regulatory cytokines/T cell subsets, and the tissue/cell type under study. Despite a spectrum of outcomes in various autoimmune diseases, mostly anti-inflammatory and immunomodulatory effects of IL-27 have been observed in this category of diseases. Accordingly, IL-27 represents a novel, promising target/agent for the treatment of autoimmune diseases.
Topics: Animals; Antigen-Presenting Cells; Autoimmunity; B-Lymphocytes; CD4-Positive T-Lymphocytes; Cell Differentiation; Humans; Interleukin-27; Lymphocyte Activation
PubMed: 26253381
DOI: 10.1016/j.autrev.2015.08.001