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Clinical and Experimental Immunology Jan 2017Immunosurveillance requires the migration of lymphocytes and their activation to induce proliferation and effector function. Effective immunity requires an optimal... (Review)
Review
Immunosurveillance requires the migration of lymphocytes and their activation to induce proliferation and effector function. Effective immunity requires an optimal supply of nutrients to lymphocytes. Cells contain nutrient sensing apparatus such as adenosine 5'-monophosphate-activated protein kinase (AMPK) that surveys intracellular ATP levels. Immunity declines during ageing and one possibility is that the energy balance may be altered in old lymphocytes. This paper summarizes recent data identifying a convergence of senescence and nutrient signalling pathways in lymphocytes that inhibit both T cell and natural killer (NK) cell function during ageing. Significantly, these pathways can be inhibited to enhance the activity of these cells.
Topics: AMP-Activated Protein Kinases; Adenosine Triphosphate; Animals; Cellular Senescence; Energy Metabolism; Humans; Immunologic Surveillance; Killer Cells, Natural; Lymphocyte Activation; Signal Transduction; T-Lymphocytes
PubMed: 27690328
DOI: 10.1111/cei.12876 -
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 -
Immunology Jun 1997Stimulation of cloned cytotoxic T lymphocytes (CTL) with anti-T-cell receptor (TCR) monoclonal antibody (mAb) in solution resulted in rapid and sustained activation of...
Stimulation of cloned cytotoxic T lymphocytes (CTL) with anti-T-cell receptor (TCR) monoclonal antibody (mAb) in solution resulted in rapid and sustained activation of adhesion to immobilized fibronectin (FN) but did not initiate degranulation. Addition of a second antibody (Ab) to further cross-link the TCR substantially increased the level of adhesion and also activated degranulation, as measured by release of serine esterase, in the presence of immobilized FN but not in its absence. Thus, binding to FN can provide a costimulatory signal to activate degranulation. TCR cross-linking also activated CD8-dependent adhesion to class I, and CD8 provided a costimulatory signal upon binding to class I. However, the requirements for activating adhesion and generating the costimulatory signal differed significantly for FN versus class I ligand, suggesting that these two receptor-ligand systems do not share a common mechanism of action. Co-immobilizing FN and alloantigen resulted in increased serine esterase release in comparison with that stimulated by antigen alone, and required the FN and class I be on the same surface. Peptide and antibody blocking demonstrated that CTL binding to FN, and to vitronectin (VN), was mediated by the alpha V beta 3 vitronectin receptor (VNR). Thus, VNR is activated by a signal from the TCR to mediate adhesion to FN or VN, and delivers a costimulatory signal for degranulation via a different mechanism than costimulation by CD8 binding to class I.
Topics: Animals; CD8-Positive T-Lymphocytes; Cell Culture Techniques; Cell Degranulation; Esterases; Fibronectins; Guinea Pigs; Lymphocyte Activation; Receptors, Antigen, T-Cell; Receptors, Vitronectin; T-Lymphocytes, Cytotoxic; Vitronectin
PubMed: 9227315
DOI: 10.1046/j.1365-2567.1997.00237.x -
British Journal of Sports Medicine Aug 2000To review results on exercise induced changes in the immune system following strenuous and moderate exercise. (Review)
Review
OBJECTIVES
To review results on exercise induced changes in the immune system following strenuous and moderate exercise.
METHODS
A literature search over the past 15 years was conducted using Medline and selected papers.
RESULTS
After intense long term exercise, the immune system is characterised by concomitant impairment of the cellular immune system and increased inflammation. Thus low concentrations of lymphocytes, suppressed natural immunity, suppressed lymphocyte proliferation, and suppressed levels of secretory IgA in saliva are found simultaneously with high levels of circulating proinflammatory and antiinflammatory cytokines. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. The clinical consequences of the exercise induced immune changes have not formally been identified, but the exercise effect on lymphocyte dynamics and immune function may be linked to the exercise effects on resistance to infections and malignancy and the cytokine response may be linked to muscle damage or muscle cell growth.
CONCLUSIONS
Moderate exercise across the life span seems to increase resistance to upper respiratory tract infections, whereas repeated strenuous exercise suppresses immune function. It is premature to offer advice on nutrition to athletes in order to alter the exercise induced immunosuppression found after exercise.
Topics: Animals; Cytokines; Exercise; Fatty Acids, Unsaturated; Glutamine; Humans; Lymphocytes
PubMed: 10953894
DOI: 10.1136/bjsm.34.4.246 -
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 -
BMC Geriatrics Mar 2021Interaction of physical activity and overall immune profile is very complex and depends on the intensity, duration and frequency of undertaken physical activity, the...
BACKGROUND
Interaction of physical activity and overall immune profile is very complex and depends on the intensity, duration and frequency of undertaken physical activity, the exposure to cytomegalovirus (CMV) infection and the age-related changes in the immune system. Daily physical activity, which particularly influences immunity, declines dramatically with age. Therefore, the aim of the study was to explain whether physical activity sustained throughout life can attenuate or reverse immunosenescence.
METHODS
Ninety-nine older adults (60-90 years) were recruited for the study. According to the 6-min walk test (6WMT), the Åstrand-Ryhming bike test (VOmax) and Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire, the individuals were classified as physically active (n = 34) and inactive (n = 20) groups. The analysis of T lymphocytes between active vs. inactive participants was performed using eight-parameter flow cytometry.
RESULTS
Analysis of the baseline peripheral naïve and memory T lymphocytes showed a significant relationship of lifestyle exercise with the CD4/CD8 ratio. Above 50% of physically active participants demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5 contrary to the inactive group who showed the ratio < 1. The older adults with the result of 6WMT > 1.3 m/s and VOmax > 35 mL/kg/min had a significantly higher CD4CD45RA T lymphocyte percentage and also a higher ratio of CD4CD45RA/CD4CD45RO. Interestingly, in active older adults with IgG CMV (n = 30) the count of CD4CD45RA T lymphocytes was higher than in the inactive group with IgG CMV (n = 20).
CONCLUSION
Based on the flow cytometry analysis, we concluded that lifestyle exercise could lead to rejuvenation of the immune system by increasing the percentage of naïve T lymphocytes or by reducing the tendency of the inverse CD4/CD8 ratio.
Topics: Aged; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Exercise; Flow Cytometry; Humans; Immunosenescence; Life Style
PubMed: 33752623
DOI: 10.1186/s12877-021-02128-7 -
Seminars in Immunology Dec 2012The mechanistic target of rapamycin (mTOR), an evolutionally conserved serine and threonine kinase, plays a critical role in the promotion of cell growth and... (Review)
Review
The mechanistic target of rapamycin (mTOR), an evolutionally conserved serine and threonine kinase, plays a critical role in the promotion of cell growth and proliferation via integration of cellular and environmental cues. In adaptive immunity, the mTOR pathway orchestrates multiple physiological processes including the development and homeostasis of T cells under steady state, and their subsequent activation and differentiation upon antigen recognition. Associated with such fate decisions is the dynamic reprogramming of T cell metabolic pathways, as naïve, activated and memory cells are defined by distinct bioenergetic and biosynthetic activities. Emerging evidence indicates that mTOR signaling intersects with T cell metabolism at two major levels to constitute a critical control mechanism of T cell fate decisions. First, as a central environmental sensor, mTOR links immune signaling and the availability of nutrients, especially amino acids. Second, mTOR activates specific metabolic pathways in T cells such as aerobic glycolysis (also known as the "Warburg effect") in a process dependent upon the induction of transcription factors MYC and HIF1α. Understanding how mTOR interplays with T cell metabolism to dictate T cell fates and functions will provide fundamental insights into the mechanism of immune responses and the development of novel therapeutics against immune-mediated diseases. In this review, we summarize the current advances on mTOR signaling and T cell metabolism in the control of development, homeostasis, activation and differentiation of T cells.
Topics: Animals; Cell Differentiation; Humans; Immunologic Memory; Lymphocyte Activation; T-Lymphocytes; TOR Serine-Threonine Kinases; Thymus Gland
PubMed: 23375549
DOI: 10.1016/j.smim.2012.12.004 -
Environmental Health Perspectives Sep 1995Results of studies of the epidemiology, physiology, histopathology, and cell biology of asthma have revised our conception of the disease. Epidemiologic studies have... (Review)
Review
Results of studies of the epidemiology, physiology, histopathology, and cell biology of asthma have revised our conception of the disease. Epidemiologic studies have shown asthma to be an important cause of death, suffering, and economic hardship. Physiologic studies have shown that asthma is a chronic illness characterized by persistent bronchial hyperreactivity. Histopathologic studies have shown characteristic changes: epithelial damage, deposition of collagen beneath the basement membrane, eosinophilic and lymphocytic infiltration, and hypertrophy and hyperplasia of goblet cells, submucosal glands, and airway smooth muscle. Studies of the functions of cells in the airway mucosa suggest that asthma may be fundamentally mediated by a difference in the type of lymphocyte predominating in the airway mucosa but may also involve complex interactions among resident and migratory cells. Asthma may thus result from sensitization of a subpopulation of CD4+ lymphocytes, the Th2 subtype, in the airways. These lymphocytes produce a family of cytokines that favor IgE production and the growth and activation of mast cells and eosinophils, arming the airways with the mechanisms of response to subsequent reexposure to the allergen. This conceptual model has stimulated research along lines that will almost certainly lead to powerful new treatments, and it has already put current therapies in a new light, clarifying the role of antinflammatory agents, especially of inhaled corticosteroids. This conceptual model has some limitations: it ignores new evidence on the role of the mast cell in producing cytokines and depends on results of studies of the effects of inhalation of allergen, although most asthma exacerbations are provoked by viral respiratory infection. Preliminary studies suggest that viral infection and allergen inhalation may involve the activation of different pathways, with viral infection activating production of cytokines by airway epithelial cells. Similar study of the mechanisms activated by inhalation of air toxics may provide important clues as to how they might induce or exacerbate asthma.
Topics: Air Pollutants; Asthma; Bronchial Hyperreactivity; Eosinophils; Humans; Lymphocytes; Models, Biological
PubMed: 8549478
DOI: 10.1289/ehp.95103s6229 -
Arthritis Research & Therapy Jan 2021Abnormalities in lymphocyte surface markers and functions have been described in systemic sclerosis (SSc), but conflicting results abound, and these studies often...
BACKGROUND
Abnormalities in lymphocyte surface markers and functions have been described in systemic sclerosis (SSc), but conflicting results abound, and these studies often examined patients with heterogeneous disease duration, severity, clinical phenotype, and concurrent immunosuppressive agents. We studied a clinically homogeneous group of early diffuse cutaneous SSc patients not exposed to immunosuppressive drugs who were enrolled in a clinical trial and compared their immune parameters to healthy control subjects.
METHODS
Lymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation.
RESULTS
SSc patients had increased percentages of CD4+ T cells but lower percentages of CD8+ T cells versus controls. The CD28-negative population was expanded in SSc, in the CD4 subset. Striking expansion of CD319+ T cells was noted among the CD4+ cells, in which they were barely detectable in healthy subjects. Frequencies of IL-4 producing cells did not differ between SSc and controls, but expansion of IL-17 producing cells was observed in SSc. A higher proportion of CD319+ cells produced cytokines, compared to other CD4+ cells. Numbers of activated T cells, regulatory T cells, and B cells were similar in SSc and control groups. Circulating follicular helper but not peripheral helper T cells were slightly expanded in SSc.
CONCLUSION
In this carefully selected group of early diffuse cutaneous SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment. The CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin, actively secrete cytokines, and are emerging as a target for novel treatments of SSc.
Topics: CD4-Positive T-Lymphocytes; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocyte Subsets; Scleroderma, Diffuse; Scleroderma, Systemic
PubMed: 33407866
DOI: 10.1186/s13075-020-02383-w -
Exercise Immunology Review 2007Lymphocytes recirculate between the blood and lymph moving by routes that take them through various lymphoid and non-lymphoid organs in order to search for their cognate... (Review)
Review
Lymphocytes recirculate between the blood and lymph moving by routes that take them through various lymphoid and non-lymphoid organs in order to search for their cognate antigen. Naïve and effector/memory T cells provide distinct repertoires of receptors and ligands that constitute their ability to interact with the microvessels of different anatomical compartments and, consequently, have distinct patterns of migration. Lymphocyte migration from vascular to extravascular sites is a tightly controlled cascade of events, initiated by tethering and rolling interactions of lymphocytes on the endothelial surface. Local chemokines initiate in the activation of integrin adhesiveness, followed by firm arrest and endothelial transmigration. Environmental stress induces a substantial re-distribution of T-cells within lymphoid and non-lymphoid organs. A uniform response pattern seems to exist with a decrease in lymphocyte numbers in the spleen which is accompanied by an increase in lymphocytes in lung, bone marrow and Peyer's patches. The alterations of the migration properties could be partially explained by adrenergic mechanisms which influence surface expression of adhesion molecules. Furthermore exercise and environmental stress result in a decreased expression of adhesion molecules, which might be the result of a selective mobilization of cells. In conclusion, exercise stress induces a substantial re-distribution of T-cells within lymphoid and non-lymphoid organs. It can be hypothesized that these stress-induced effects on lymphocyte trafficking might enhance immune surveillance and vigilance. However, further investigations are crucially needed to gain more insights into the underlying mechanisms.
Topics: Animals; Cell Movement; Exercise; Exercise Test; Humans; Signal Transduction; T-Lymphocytes
PubMed: 18198659
DOI: No ID Found