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Biomedicine & Pharmacotherapy =... Dec 2018This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of...
This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of lymphocytes, IL-6 and IL-10 levels and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) activity in rat lymphocytes. The animals were divided into groups: control, caffeine 4 mg/kg, caffeine 8 mg/kg, HIIT, HIIT plus caffeine 4 mg/kg and HIIT plus caffeine 8 mg/kg. The rats were trained three times a week for 6 weeks for a total workload 23% of body weight at the end of the experiment. Caffeine was administered orally 30 min before the training session. When lymphocytes were stimulated with phytohaemagglutinin no changes were observed in proliferative response between trained and sedentary animals; however, when caffeine was associated with HIIT an increase in T lymphocyte proliferation and in the sensitivity of lymphocytes to glucocorticoids occurred. ATP and ADP hydrolysis was decreased in the lymphocytes of the animals only trained and caffeine treatment prevented alterations in ATP hydrolysis. HIIT caused an increase in the ADA and AChE activity in lymphocytes and this effect was more pronounced in rats trained and supplemented with caffeine. The level of IL-6 was increased while the level of IL-10 was decreased in trained animals (HIIT) and caffeine was capable of preventing this exercise effect. Our findings suggest that caffeine ingestion attenuates, as least in part, the immune and inflammatory alterations following a prolonged HIIT protocol.
Topics: Acetylcholinesterase; Adenosine; Adenosine Deaminase; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Caffeine; Cell Proliferation; Cytokines; Glucocorticoids; Hydrolysis; Lymphocyte Activation; Lymphocytes; Male; Physical Conditioning, Animal; Rats, Wistar; Receptors, Cholinergic; Receptors, Purinergic; Signal Transduction
PubMed: 30372876
DOI: 10.1016/j.biopha.2018.10.006 -
British Journal of Haematology Oct 2007Toll-like receptors (TLRs) play a critical role in the induction of the immune response to invading pathogens. The detection of pathogens by TLRs initiates a signalling... (Review)
Review
Toll-like receptors (TLRs) play a critical role in the induction of the immune response to invading pathogens. The detection of pathogens by TLRs initiates a signalling cascade that results in the activation of transcription factors such as nuclear factor (NF)-kappaB and interferon regulatory factors leading to the production of pro-inflammatory cytokines and type 1 interferons. Five cytoplasmic adaptors, MyD88, Mal, Trif, TRAM and SARM, are utilized by the TLRs to activate these signalling pathways. Through the years the main focus of research has been on the activation and function of TLRs in monocytic cells. This review discusses several additional roles of TLRs. TLR activation plays a role in influencing the differentiation of haematopoietic stem cells. Their activation also prevents apoptosis in neutrophils following pathogen invasion. B cells and T cells proliferation and differentiation is influenced by TLR activation and the possible therapeutic benefits of using TLR ligands for the treatment of chronic lymphocytic leukaemia will also be discussed.
Topics: Apoptosis; Hematopoiesis; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocyte Activation; Lymphocytes; Neutrophils; Toll-Like Receptors
PubMed: 17897294
DOI: 10.1111/j.1365-2141.2007.06802.x -
Veterinary Immunology and... Nov 2015Monoclonal antibodies (mAbs) specific for leukocyte differentiation molecules (LDMs) were developed during the past few decades to expand reagents for research in...
Monoclonal antibodies (mAbs) specific for leukocyte differentiation molecules (LDMs) were developed during the past few decades to expand reagents for research in ruminants, pigs, and horses. The specificity of some of the mAb-defined molecules was determined through participation in international workshops. Other molecules identified with mAbs during this time, and more recently with mAbs developed after the workshops, have remained partially characterized. Efforts are now underway to characterize the specificity of these mAbs. As reported here, flow cytometry (FC) was used to screen two sets of hybridomas to determine how many of the hybridomas produce mAbs that detect molecules with up-regulated expression on activated lymphocytes or NK cells. Thirty four hybridomas were identified. Comparison of the patterns of reactivity of the mAbs showed some of the mAbs formed clusters that recognize 5 different molecules. FC showed one cluster recognized CD25. Use of mass spectrometry showed 4 clusters recognized orthologues of CD26, CD50, gp96 and signaling lymphocytic activation molecule family member 9 (SLAMF9). Verification and documentation that CD26, CD50, and SLAMF9 were only up-regulated on activated cells was obtained with PBMC from calves vaccinated with a Mycobacterium avium paratuberculosis mutant, Map-relA. CD26 and CD50 were up-regulated on NK cells, CD4 and CD8 T cells and γδ T cells. SLAMF9 was only up-regulated on CD4, CD8, and γδ T cells. gp96 was detected on granulocytes, monocytes and activated NK cells. Detection was attributable to the binding of gp96 to its receptor CD91.
Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Antigens, CD; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cattle; Dipeptidyl Peptidase 4; Interleukin-2 Receptor alpha Subunit; Killer Cells, Natural; Lymphocyte Activation; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Cell Surface; Signaling Lymphocytic Activation Molecule Family Member 1; T-Lymphocyte Subsets
PubMed: 26384699
DOI: 10.1016/j.vetimm.2015.09.002 -
Exercise Immunology Review 2019Individuals with amnestic mild cognitive impairment (aMCI) experience cognitive declines in learning and memory greater than expected for normal aging, and are at a high... (Review)
Review
T and B cell subsets differentially correlate with amyloid deposition and neurocognitive function in patients with amnestic mild cognitive impairment after one year of physical activity.
Individuals with amnestic mild cognitive impairment (aMCI) experience cognitive declines in learning and memory greater than expected for normal aging, and are at a high risk of dementia. We previously reported that sedentary aMCI patients exhibited neuroinflammation that correlated with brain amyloid beta (Aβ) burden, as determined by 18F-florbetapir positron emission tomography (PET). These aMCI patients enrolled in a one-year randomized control trial (AETMCI, NCT01146717) to test the beneficial effects of 12 months of moderate-to-high intensity aerobic exercise training (AET) or stretching/toning (ST) control intervention on neurocognitive function. A subset of aMCI participants had PET imaging, cognitive testing, and immunophenotyping of cerebrospinal fluid (CSF) and peripheral blood after AET or ST interventions. As adaptive immune responses were similar between AET and ST groups, we combined AET/ST into a general 'physical activity' (PA) group and compared Aβ burden, cognitive function, and adaptive immune cell subsets to sedentary lifestyle before intervention. We found that PAinduced immunomodulation of CD4+ and CD8+ T cells in CSF correlated with changes in Aβ burden in brain regions associated with executive function. Furthermore, after PA, cognitive scores on tests of memory, processing speed, attention, verbal fluency, and executive function were associated with increased percent representation of circulating naïve B + T cells. We review the literature on aMCI-related cognition and immune changes as they relate to exercise, and highlight how our preliminary data suggest a complex interplay between the adaptive immune system, physical activity, cognition, and Aβ burden in aMCI.
Topics: Adaptive Immunity; Amyloid beta-Peptides; B-Lymphocyte Subsets; Cognitive Dysfunction; Exercise; Humans; Randomized Controlled Trials as Topic; T-Lymphocyte Subsets
PubMed: 30785868
DOI: No ID Found -
Frontiers in Bioscience (Elite Edition) Jan 2010While the stress associated with acute exercise has been reported to induce significant lymphocyte apoptosis, not all investigations have confirmed this finding.... (Review)
Review
While the stress associated with acute exercise has been reported to induce significant lymphocyte apoptosis, not all investigations have confirmed this finding. Regardless of animal or human subjects, exercise-induced lymphocyte apoptosis may be induced via an external receptor-mediated pathway, or internally via the mitochondria through an oxidative-mediated pathway. On the other hand, investigators reporting no effect of acute exercise on lymphocyte apoptosis speculate that cell death may be dissociated from these pathways, and explain exercise lymphocytopenia by selective migration of the lymphocytes back into the lymphoid pools. Discrepancies may be due to sensitivity issues related to the methodology used to assess cell death. Limitations to various methods used to evaluate exercise-induced lymphocyte apoptosis are detailed, and considerations for a new technique are outlined.
Topics: Animals; Apoptosis; Exercise; Humans; Lymphocytes; Lymphopenia; Mice; Rats; Stress, Physiological
PubMed: 20036894
DOI: 10.2741/e106 -
Clinical & Developmental Immunology 2011Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like... (Review)
Review
Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like receptor (TLR) ligands and an NKT cell ligand (α-galactocylceramide), activate liver Kupffer cells, which produce IL-1, IL-6, IL-12, and TNF. IL-12 activates hepatic NK cells and NKT cells to produce IFN-γ, which further activates hepatic T cells, in turn activating phagocytosis and cytokine production by Kupffer cells in a positive feedback loop. These immunological events are essentially evoked to protect the host from bacterial and viral infections; however, these events also contribute to antitumor and antimetastatic immunity in the liver by activated liver NK cells and NKT cells. Bystander CD8(+)CD122(+) T cells, and tumor-specific memory CD8(+)T cells, are also induced in the liver by α-galactocylceramide. Furthermore, adoptive transfer experiments have revealed that activated liver lymphocytes may migrate to other organs to inhibit tumor growth, such as the lungs and kidneys. The immunological mechanism underlying the development of hepatocellular carcinoma in cirrhotic livers in hepatitis C patients and liver innate immunity as a double-edged sword (hepatocyte injury/regeneration, septic shock, autoimmune disease, etc.) are also discussed.
Topics: Aging; Animals; Bacteria; CD8-Positive T-Lymphocytes; Galactosylceramides; Hepatocytes; Humans; Interleukin-12; Interleukin-2 Receptor beta Subunit; Killer Cells, Natural; Kupffer Cells; Liver Neoplasms; Lymphocyte Activation; Multiple Organ Failure; Natural Killer T-Cells; Neoplasms; Shock, Septic; T-Lymphocytes, Cytotoxic
PubMed: 22190974
DOI: 10.1155/2011/868345 -
Frontiers in Immunology 2019B lymphocytes, as a central part of adaptive immune responses, have the ability to fight against an almost unlimited numbers of pathogens. Impairment of B cell...
B lymphocytes, as a central part of adaptive immune responses, have the ability to fight against an almost unlimited numbers of pathogens. Impairment of B cell development, activation and differentiation to antibody secreting plasma cells can lead to malignancy, allergy, autoimmunity and immunodeficiency. However, the impact of environmental factors, such as hyperosmolality or osmotic stress caused by varying salt concentrations in different lymphoid organs, on these processes is not well-understood. Here, we report that B cells respond to osmotic stress in a biphasic manner. Initially, increased osmolality boosted B cell activation and differentiation as shown by an untimely downregulation of Pax5 as well as upregulation of CD138. However, in the second phase, we observed an increase in cell death and impaired plasmablast differentiation. Osmotic stress resulted in impaired class switch to IgG1, inhibition of phosphorylation of p38 mitogen-activated kinase and a delayed NFAT5 response. Overall, these findings demonstrate the importance of microenvironmental hyperosmolality and osmotic stress caused by NaCl for B cell activation and differentiation.
Topics: Animals; B-Lymphocytes; Cell Differentiation; Cells, Cultured; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred C57BL; Osmolar Concentration; Phosphorylation; p38 Mitogen-Activated Protein Kinases
PubMed: 31057551
DOI: 10.3389/fimmu.2019.00828 -
Life Sciences Jul 1983Mood states and immunity may be related. To investigate the immune status of patients with primary depressive illness, we compared in-vitro lymphocytic responses to... (Comparative Study)
Comparative Study
Mood states and immunity may be related. To investigate the immune status of patients with primary depressive illness, we compared in-vitro lymphocytic responses to three different mitogens in 26 drug-free depressed patients and 20 normal controls of comparable age and sex. We observed a generalized and marked decrease in the lymphocyte mitogenic activity among the depressive group. This defect in lymphocyte function may be indicative of an impairment in cell-mediated immunity in patients with primary depressive illness.
Topics: Adult; Aged; Cells, Cultured; Depressive Disorder; Dose-Response Relationship, Immunologic; Female; Humans; Immunity, Cellular; Lymphocytes; Male; Middle Aged; Mitogens
PubMed: 6865657
DOI: 10.1016/0024-3205(83)90382-x -
Advances in Clinical and Experimental... Jul 2018Chronic lymphocytic leukemia (CLL) is a condition characterized by the accumulation of morphologically mature monoclonal lymphocytes B with the CD19+/CD5+/CD23+...
Relationship between the expression of CD25 and CD69 on the surface of lymphocytes T and B from peripheral blood and bone marrow of patients with chronic lymphocytic leukemia and established prognostic factors of this disease.
BACKGROUND
Chronic lymphocytic leukemia (CLL) is a condition characterized by the accumulation of morphologically mature monoclonal lymphocytes B with the CD19+/CD5+/CD23+ phenotype in lymphoid tissue, peripheral blood and bone marrow. The clinical course of patients with CLL is heterogeneous, ranging from indolent to aggressive. The role of lymphocyte activation in the natural history of CLL is still a matter of discussion.
OBJECTIVES
The aim of this study was to determine the percentages and absolute numbers of lymphocytes B and T in peripheral blood and bone marrow of CLL patients. Moreover, we analyzed the relationship between the number of CD25-positive and CD69-positive lymphocytes and the established prognostic factors in CLL.
MATERIAL AND METHODS
The study included 80 untreated patients with CLL and 20 healthy subjects. The immunophenotype of peripheral blood mononuclear cells (in both groups) and bone marrow cells (solely in the CLL group) was determined by means of flow cytometry.
RESULTS
Patients with CLL showed a higher absolute number of activated lymphocytes B with phenotypes CD19+CD25+ and CD19+CD69+, as well as a higher absolute number of CD3+CD25+ lymphocytes T than the controls. The enhanced activation of peripheral blood and bone marrow lymphocytes was associated with higher Rai stages, an increased concentration of lactate dehydrogenase and beta-2 microglobulin and the progression of the disease. The number of lymphocytes B CD19+ZAP-70+ correlated positively with the number of CD19+CD25+ B cells and CD3+CD69+ T cells.
CONCLUSIONS
The study confirmed the association between an unfavorable prognosis and a high expression of activation markers in CLL patients. The determination of CD25+ and CD69+ lymphocytes T and B constitutes a valuable diagnostic tool, completing the cytometric evaluation of CLL.
Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; B-Lymphocytes; Female; Humans; Interleukin-2 Receptor alpha Subunit; Lectins, C-Type; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets; Male; Middle Aged; Prognosis; T-Lymphocytes
PubMed: 29893517
DOI: 10.17219/acem/74437 -
PloS One 2016Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The...
Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations- 1 μM (10(-3) mol/m(3)), 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD). The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA]) was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance-expansion of Treg cells and lymphocyte apoptosis-was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog.
Topics: Animals; Antigens, CD; Apoptosis; Cell Proliferation; Cell Survival; Dogs; Forkhead Transcription Factors; Gene Expression Regulation; Lymphocyte Activation; Lymphocytes; Mycophenolic Acid; Proliferating Cell Nuclear Antigen
PubMed: 27138877
DOI: 10.1371/journal.pone.0154429