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Exercise and Sport Sciences Reviews Jul 2017Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy are effective in treating blood cancers and posttransplant infections, but... (Review)
Review
Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy are effective in treating blood cancers and posttransplant infections, but low-circulating cell numbers in patients and donors are oftentimes a limiting factor. We postulate that a single exercise bout will increase the yield of patient- and donor-derived HSCs and cytotoxic lymphocytes to improve this form of treatment for cancer patients.
Topics: Exercise; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Killer Cells, Natural; Lymphocyte Count; Neoplasms; T-Lymphocytes
PubMed: 28418996
DOI: 10.1249/JES.0000000000000114 -
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 -
Biochemical and Biophysical Research... Apr 2021T cells secrete several inflammatory cytokines that play a critical role in the progression of atherosclerosis. Although green tea epigallocatechin-3-gallate (EGCG)...
T cells secrete several inflammatory cytokines that play a critical role in the progression of atherosclerosis. Although green tea epigallocatechin-3-gallate (EGCG) exerts anti-inflammatory and anti-atherosclerotic effects in animals, few studies have identified the mechanism underlying these effects in human primary T cells. This study investigated the pathway involved in EGCG modulation of cytokine secretion in activated human primary T cells. We pre-treated human primary T cells with EGCG (0.1, 1, 5, 10, and 20 μM) for 4 h and incubated them with or without phorbol 12-myristate 13-acetate and ionomycin (P/I) for 20 h. The cytokine production, activator protein (AP)-1 binding activity, and level of mitogen-activated protein kinase (MAPK) were assessed using enzyme-linked immunosorbent assay, electrophoretic mobility shift assay, and Western blotting, respectively. At 10 and 20 μM, EGCG decreased interleukin (IL)-2 levels by 26.0% and 38.8%, IL-4 levels by 41.5% and 55.9%, INF-γ levels by 31.3% and 34.7%, and tumor-necrosis factor (TNF)-α levels by 23.0% and 37.6%, respectively. In addition, the level of phosphorylated c-Jun N-terminal (p-JNK) and extracellular signal-regulated kinase (p-ERK) was decreased, but not the level of p-p38 MAPK. EGCG did not alter any of the total protein amounts, suggesting a selective effect on specific types of MAPKs in stimulated human T cells. EGCG tended to inactivate AP-1 DNA-binding activity. The P/I-induced production of IL-2, IL-4, INF-γ, and TNF-α by human T cells was suppressed by AP-1 inhibitor in a concentration-dependent manner. In conclusion, EGCG suppressed cytokine secretion in activated human primary T cells, and this effect was likely mediated by AP-1 inactivation through the ERK and JNK, but not p38 MAPK, pathways. These results may be related to the mechanisms through which EGCG inhibits immune- or inflammation-related atherogenesis.
Topics: Anti-Inflammatory Agents; Catechin; Cell Survival; Cells, Cultured; Cytokines; Down-Regulation; Humans; Inflammation; Lymphocyte Activation; MAP Kinase Signaling System; T-Lymphocytes; Transcription Factor AP-1
PubMed: 33689882
DOI: 10.1016/j.bbrc.2021.02.132 -
Frontiers in Immunology 2019Traditional tumor vaccination approaches mostly focus on activating dendritic cells (DCs) by providing them with a source of tumor antigens and/or adjuvants, which in... (Review)
Review
Traditional tumor vaccination approaches mostly focus on activating dendritic cells (DCs) by providing them with a source of tumor antigens and/or adjuvants, which in turn activate tumor-reactive T cells. Novel biomaterial-based cancer immunotherapeutic strategies focus on directly activating and stimulating T cells through molecular cues presented on synthetic constructs with the aim of improving T cell survival, more precisely steer T cell activation and direct T cell differentiation. Synthetic artificial antigen presenting cells (aAPCs) decorated with T cell-activating ligands are being developed to induce robust tumor-specific T cell responses, essentially bypassing DCs. In this perspective, we approach these promising new technologies from an immunological angle, first by identifying the CD4 and CD8 T cell subtypes that are imperative for robust anti-cancer immunity and subsequently discussing the molecular cues needed to induce these cells types. We will elaborate on how biomaterials can be applied to stimulate T cells and to improve their survival, activation and function. Scaffold-based methods can also be used as delivery vehicles for adoptive transfer of T cells, including tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor expressing (CAR) T cells, while simultaneously stimulating these cells. Finally, we provide suggestions on how these insights could advance the field of biomaterial-based activation and expansion of tumor-specific T cells in the future.
Topics: Animals; Biocompatible Materials; Humans; Immunotherapy; Neoplasms; T-Lymphocytes
PubMed: 31130945
DOI: 10.3389/fimmu.2019.00931 -
British Journal of Haematology Jul 2019Chronic lymphocytic leukaemia (CLL) has long been thought to be an immunosuppressive disease and abnormalities in T-cell subset distribution and function have been... (Review)
Review
Chronic lymphocytic leukaemia (CLL) has long been thought to be an immunosuppressive disease and abnormalities in T-cell subset distribution and function have been observed in many studies. However, the role of T cells (if any) in disease progression remains unclear and has not been directly studied. This has changed with the advent of new therapies, such as chimeric antigen receptor-T cells, which actively use retargeted patient-derived T cells as "living drugs" for CLL. However complete responses are relatively low (~26%) and recent studies have suggested the differentiation status of patient T cells before therapy may influence efficacy. Non-chemotherapeutic drugs, such as idelalisib and ibrutinib, also have an impact on T cell populations in CLL patients. This review will highlight what is known about T cells in CLL during disease progression and after treatment, and discuss the prospects of using T cells as predictive biomarkers for immune status and response to therapy.
Topics: Adenine; B-Lymphocytes; Humans; Immunotherapy, Adoptive; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Purines; Pyrazoles; Pyrimidines; Quinazolinones; T-Lymphocyte Subsets
PubMed: 30945268
DOI: 10.1111/bjh.15918 -
Veterinary Immunology and... May 2020CellTrace Violet™ is a commonly used fluorescent dye used with flow cytometry to identify cell proliferation. Activated equine lymphocytes were examined using flow...
CellTrace Violet™ is a commonly used fluorescent dye used with flow cytometry to identify cell proliferation. Activated equine lymphocytes were examined using flow cytometry, microscopy and tritiated thymidine proliferation assays. CellTrace Violet™ was incorporated into the equine lymphocytes effectively. Equine lymphocytes proliferated when activated with pokeweed mitogen, but did not proliferate when previously stained with CellTrace Violet™. Serial dilutions of CellTrace Violet™ did not eliminate the inhibition of activated lymphocytes. Equine lymphocyte viability was greater than 90 % for both stained and unstained cells. Based on these data, CellTrace Violet™ is not recommended for the assessment of lymphocyte proliferation in equine cells. The mechanism of inhibition of equine lymphocyte proliferation by CellTrace Violet™ is unknown.
Topics: Animals; Cell Proliferation; Cell Survival; Concanavalin A; Flow Cytometry; Fluorescent Dyes; Horses; Lymphocyte Activation; Lymphocytes; Pokeweed Mitogens
PubMed: 32229340
DOI: 10.1016/j.vetimm.2020.110037 -
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 -
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