-
Virology Jan 2020In addition to direct anti-viral activity, NK cells regulate viral pathogenesis by virtue of their cytolytic attack on activated CD4 and CD8 T cells. To gain insight...
In addition to direct anti-viral activity, NK cells regulate viral pathogenesis by virtue of their cytolytic attack on activated CD4 and CD8 T cells. To gain insight into which differentiated T cell subsets are preferred NK targets, transgenic T cells were differentiated in vitro into Th0, Th1, Th2, Th17, Treg, Tc1, and Tc2 effector cells and then tested for lysis by enriched populations of lymphocytic choriomeningitis virus (LCMV)-induced activated NK cells. There was a distinct hierarchy of cytotoxicity in vitro and in vivo, with Treg, Th17, and Th2 cells being more sensitive and Th0 and Th1 cells more resistant. Some distinctions between in vitro vs in vivo generated T cells were explainable by type 1 interferon induction of class 1 histocompatibility antigens on the effector T cell subsets. NK receptor (NKR)-deficient mice and anti-NKR antibody studies identified no one essential NKR for killing, though there could be redundancies.
Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Interferons; Killer Cells, Natural; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, Natural Killer Cell; T-Lymphocyte Subsets
PubMed: 31670188
DOI: 10.1016/j.virol.2019.10.003 -
Neurorehabilitation and Neural Repair Jun 2016Background In a combined animal and human study, we have previously found that a 5-day treatment that enhances cortical plasticity also facilitates brain-derived...
Background In a combined animal and human study, we have previously found that a 5-day treatment that enhances cortical plasticity also facilitates brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling and increases activated TrkB and N-methyl-d-aspartate receptor (NMDAR) association in both the cortex and the peripheral lymphocytes. Patients with Parkinson's disease (PD), in general, show decreased cortical plasticity, as demonstrated by electrophysiological and behavioral studies. Here, we test the hypothesis that an exercise program that improves motor function and seems to slow down symptom progression can enhance BDNF-TrkB signaling in lymphocytes. Methods A total of 16 patients with PD underwent a 4-week multidisciplinary intensive rehabilitation treatment (MIRT), which included aerobic training and physical and occupational therapy. Blood was collected before and after 2 and 4 weeks of MIRT. Lymphocytes were isolated to examine BDNF-TrkB signaling induced by incubation with recombinant human BDNF. TrkB signaling complexes, extracellular-signal-regulated kinase-2 and protein-kinase-B were immunoprecipitated; the content of immunocomplexes was determined by Western blotting. Results After MIRT, all patients showed improvement in motor function. TrkB interaction with NMDAR and BDNF-TrkB signaling increased in peripheral lymphocytes at receptor, intracellular mediator, and downstream levels. The decrements in Unified Parkinson's Disease Rating Scale II (UPDRSII) and total scores were significantly correlated with the increases in TrkB signaling at receptor, intracellular mediator, and NMDAR interaction levels. Conclusions The significant correlation between reduced UPDRS scores and the changes in lymphocyte activity suggest that enhanced BDNF-TrkB signaling in lymphocyte and reduced severity of PD symptoms may be related.
Topics: Aged; Aged, 80 and over; Brain-Derived Neurotrophic Factor; Exercise; Female; Follow-Up Studies; Gene Expression Regulation; Humans; Lymphocytes; Male; Middle Aged; Occupational Therapy; Parkinson Disease; Physical Therapy Modalities; Receptor, trkB; Severity of Illness Index; Signal Transduction
PubMed: 26253177
DOI: 10.1177/1545968315600272 -
Cell Adhesion & Migration 2011Coordinated changes of actin cytoskeleton and cell adhesion accompany maturation of lymphoid cells, their migration through lymphoid organs and to sites of inflammation,... (Review)
Review
Coordinated changes of actin cytoskeleton and cell adhesion accompany maturation of lymphoid cells, their migration through lymphoid organs and to sites of inflammation, as well as metastasis of transformed cells. Here we discuss the central role of the actin-regulating adaptor protein, paxillin, during lymphocyte transition from a polarized, motile cell phenotype with partially active LFA-1 integrins to a round and immobile one with fully active LFA-1. In Baf3 murine pro-B lymphocytes, the former phenotype is induced by IL-3 that stimulates a FAK-mediated phosphorylation of paxillin at tyrosines (Y) 31 and 118 and a consequent Rac1 activation. Rearrangements of actin cytoskeleton that lead to the cell's acquisition of a spherical shape and LFA-1 activation are achieved upon activation of PKC-δ that binds and directly phosphorylates paxillin at threonine (T) 538 with consequent RhoA activation. This is accompanied by dephosphorylation of paxillin Y31/118 and by Rac1 inactivation. We propose a model of signaling cascades that reflects the interplay between the IL-3- and PKC-δ-mediated pathways.
Topics: Actin Cytoskeleton; Animals; Cell Movement; Humans; Lymphocyte Function-Associated Antigen-1; Lymphocytes; Paxillin; Phosphorylation; Protein Kinase C-delta; Protein Multimerization; Protein Processing, Post-Translational; Signal Transduction
PubMed: 22274710
DOI: 10.4161/cam.5.6.18219 -
Communications Biology Jun 2022T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This...
T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This form of regulation has been well-studied within a given T cell population - i.e., within the naïve or memory pool; however, less is known about the cross-talk between T cell subsets. Here, we tested whether memory T cells interact with and influence surrounding naïve T cells. We report that human naïve CD8 T cells (T) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (T). Following in vitro co-culture with activated central memory cells (T), ~3% of the T acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that ~3% of the T acquired an activated/memory signature, while ~84% developed a unique activated transcriptional profile hybrid between naïve and activated memory. Pseudotime trajectory analysis provided further evidence that T with an activated/memory or hybrid phenotype were derived from T. Our data reveal a non-cytotoxic function of T with potential to activate autologous T into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation.
Topics: CD8-Positive T-Lymphocytes; Humans; Immunologic Memory; Memory T Cells; T-Lymphocyte Subsets
PubMed: 35768564
DOI: 10.1038/s42003-022-03596-2 -
Exercise Immunology Review 2005In the search for tumor-specific antigens, microbial and eukaryotic heat shock proteins (HSP) have been identified. Intracellularly, HSPs function as molecular... (Review)
Review
In the search for tumor-specific antigens, microbial and eukaryotic heat shock proteins (HSP) have been identified. Intracellularly, HSPs function as molecular chaperones supporting folding and transport of a great variety of polypeptides and proteins under normal physiological conditions and following stress stimuli. Furthermore, interferon-gamma and elevated body temperature induced by exercise have been found to increase serum levels of HSPs in humans. Extracellularly localized or plasma membrane-bound HSPs elicit a potent anti-cancer immune response mediated either by the adaptive or innate immune system. Following uptake of HSP (HSP70 and gp96)-peptide complexes by antigen presenting cells (APCs) and "cross-presentation" of HSP-chaperoned peptides on MHC class I molecules, a CD8-specific T cell response is induced. Apart from chaperoning tumor-specific peptides, HSPs per se provide activatory signals for the innate immune system. Binding of peptide-free HSP70 to APCs via Toll-like receptors (TLRs) initiates the secretion of pro-inflammatory cytokines and thus results in a broad non-specific immunostimulation. An unusual membrane localization of Hsp70, the major heat-inducible member of the HSP70 family, on tumor cells but not on corresponding normal tissues was found to act as a tumor-specific recognition structure for natural killer (NK) cells. Soluble as well as cell membrane-bound HSP70 can directly activate the cytolytic and migratory capacity of NK cells. APCs and tumor cells actively release HSP70s in lipid vesicles with biophysical properties of exosomes. These HSP70-presenting exosomes are thought to stimulate the adaptive and innate immune system in vivo. Taken together, depending on their intra/extracellular localization, peptide loading status, origin and route of application, HSPs either exert immune activation as danger signals in cancer immunity or protect cells from lethal damage induced by exogenous stress stimuli.
Topics: CD8-Positive T-Lymphocytes; Cell Membrane; Exercise; Extracellular Space; HSP70 Heat-Shock Proteins; Humans; Immunologic Factors; Killer Cells, Natural; Models, Biological; Neoplasms; Signal Transduction
PubMed: 16385841
DOI: No ID Found -
The American Journal of Pathology Nov 1976Mononuclear phagocytes secrete a number of materials into the extracellular environment. The materials secreted by phagocytes can be grouped into three categories: a)... (Review)
Review
Mononuclear phagocytes secrete a number of materials into the extracellular environment. The materials secreted by phagocytes can be grouped into three categories: a) enzymes affecting extracellular proteins (collagenase, elastase, lysosomal proteases, plasminogen activators), b) materials involved in defense processes (complement proteins, interferons, lysozyme), and c) factors regulating activities of surrounding cells. The latter include lymphostimulatory molecules, a colony-stimulating factor, and inhibitors of cell growth. The conditions for secretion of the materials depend on the activity of the phagocytes. The lymphostimulatory molecules secreted by macrophages exert various effects: 1) an increase in DNA synthesis of lymphocytes, 2) a maturation of early thymocytes to mature T cells, and 3) the differentiation of some B cells to antibody-secreting cells. The mitogenic principle has been partially isolated as a protein of 15,000 to 20,000 daltons. The secretion of lymphostimulatory molecules is increased following uptake of various materials by macrophages or by addition of activated T cells to macrophage cultures.
Topics: Animals; B-Lymphocytes; Enzymes; Fluoresceins; Haptens; Hemocyanins; Humans; Immunity, Cellular; Inflammation; Lectins; Listeria; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Lysosomes; Macrophages; Phagocytes; Spleen; T-Lymphocytes
PubMed: 136901
DOI: No ID Found -
International Journal of Molecular... Feb 2021Pseurotins, a family of secondary metabolites of different fungi characterized by an unusual spirocyclic furanone-lactam core, are suggested to have different biological...
BACKGROUND
Pseurotins, a family of secondary metabolites of different fungi characterized by an unusual spirocyclic furanone-lactam core, are suggested to have different biological activities including the modulation of immune response.
PURPOSE
Complex characterization of the effects of pseurotin D on human lymphocyte activation in order to understand the potential of pseurotin to modulate immune response in humans.
METHODS
CD4+ and CD8+ T cells and CD19+ B cells isolated from human blood were activated by various activators simultaneously with pseurotin D treatment. The effects of pseurotin were tested on the basis of changes in cell viability, apoptosis, activation of signal transducers and activators of transcription (STAT) signaling pathways, production of tumor necrosis factor (TNF)-α by T cells, expression of activation markers CD69 and CD25 on T cells and Human Leukocyte Antigen-DR isotype (HLA-DR) on B cells, and the differentiation markers CD20, CD27, CD38, and immunoglobulin (Ig) D on B cells.
RESULTS
Pseurotin D significantly inhibited the activation of both CD4+ and CD8+ human T cells complemented by the inhibition of TNF-α production without significant acute toxic effects. The Pseurotin D-mediated inhibition of T-cell activation was accompanied by the induction of the apoptosis of T cells. This corresponded with the inhibited phosphorylation of STAT3 and STAT5. In human B cells, pseurotin D did not significantly inhibit their activation; however, it affected their differentiation.
CONCLUSIONS
Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of lymphocytes and suggest pseurotins as new attractive chemotypes for future research in the context of immune-modulatory drugs.
Topics: Adolescent; Adult; Antigens, CD19; Apoptosis; B-Lymphocytes; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Differentiation; Cells, Cultured; Female; Healthy Volunteers; Humans; Immunologic Factors; Lymphocyte Activation; Male; Middle Aged; Pyrrolidinones; Signal Transduction; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 33669259
DOI: 10.3390/ijms22041938 -
Biophysical Journal Sep 2020
Topics: Amoeba; Animal Fins; Animals; Biomechanical Phenomena; Lymphocytes; Swimming
PubMed: 32853560
DOI: 10.1016/j.bpj.2020.08.006 -
PloS One 2016This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young... (Clinical Trial)
Clinical Trial
This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important and requires further investigation.
Topics: Apoptosis; Biomarkers; Cell Proliferation; Cell Survival; Cytokines; Exercise; Gene Expression Regulation; Heart Rate; Humans; Lymphocytes; Male; Oxidation-Reduction; Young Adult
PubMed: 27096389
DOI: 10.1371/journal.pone.0153647 -
Journal of the American Society of... Jan 2017
Topics: Exercise; Glomerulonephritis; T-Lymphocytes, Regulatory
PubMed: 27683895
DOI: 10.1681/ASN.2016070785