scholarly journals The Increase of Circulating PD-1- and PD-L1-Expressing Lymphocytes in Endometriosis: Correlation with Clinical and Laboratory Parameters

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Monika Walankiewicz ◽  
Ewelina Grywalska ◽  
Grzegorz Polak ◽  
Izabela Korona-Glowniak ◽  
Elzbieta Witt ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Flow Cytometric Analysis ◽  
Peripheral Tolerance ◽  
Cell Mediated Immunity ◽  
T And B Cells ◽  
Inhibitory Function ◽  
Flow Cytometric

The cause of endometriosis remains unknown. However, studies investigating the link between this condition and the immune system revealed several immunological abnormalities focused on cell-mediated immunity. As a major immune checkpoint, programmed cell death protein 1 (PD-1) displays an important inhibitory function in the maintenance of peripheral tolerance. The expression of PD-1 and its ligand (PD-L1) may contribute to continuous T cell activation and development of inflammation and injury of the tissue. To our knowledge, this is the first study evaluating frequencies of PD-1-positive T CD3+ cells (CD4+ and CD8+) and B cells (CD19+) in patients with endometriosis. Peripheral blood (PB) samples from 25 female patients and 20 healthy age and sex-matched subjects serving as controls were used in the study. Using flow cytometric analysis, we assessed the differences in the frequencies of PD-1-positive T and B lymphocytes in the study group and healthy individuals. Alteration of the PD-1/PD-L1 axis may contribute to the pathogenesis of endometriosis, as patients with advanced disease are characterized by higher frequencies of PD-1-positive T and B cells. Expression of PD-1 and PD-L1 on T and B cells could represent the hallmark of immune system reaction to chronic antigenic exposition in patients with endometriosis.

scholarly journals CD4+ T cell activation and tolerance induction in B cell knockout mice.

1996 ◽  
Vol 183 (4) ◽  
pp. 1339-1344 ◽  
Author(s):  
J A Phillips ◽  
C G Romball ◽  
M V Hobbs ◽  
D N Ernst ◽  
L Shultz ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Knockout Mice ◽  
Cell Activation ◽  
Peripheral Tolerance ◽  
Cd4 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance

B cell knockout mice microMT/microMT were used to examine the requirement for B cell antigen (Ag) presentation in the establishment of CD4+ T cell tolerance. CD4+T cells from microMT mice injected with exogenous protein Ag in adjuvant responded to in vitro challenge by transcription of cytokine mRNA, cytokine secretion, and proliferation. Peripheral tolerance could be established in microMT mice with a single dose of deaggragated protein. This tolerance was manifested by a loss of T cell proliferation and cytokine production (including both T helper cell type 1 [Th1]- and Th2-related cytokines), indicating that B cells are not required for the induction of peripheral T cell tolerance and suggesting that the dual zone tolerance theory is not applicable to all protein Ags and is not mediated through Ag presentation by B cells.

scholarly journals Expression and Function of Tec, Itk, and Btk in Lymphocytes: Evidence for a Unique Role for Tec

2004 ◽  
Vol 24 (6) ◽  
pp. 2455-2466 ◽  
Author(s):  
Michael G. Tomlinson ◽  
Lawrence P. Kane ◽  
Jennifer Su ◽  
Theresa A. Kadlecek ◽  
Marianne N. Mollenauer ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Th2 Cells ◽  
Receptor Signaling ◽  
T And B Cells ◽  
Nfat Activation ◽  
Cell Receptor Signaling

ABSTRACT The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. Btk is essential for B-cell receptor signaling, because mutations in Btk are responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice, whereas Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, but its role in antigen receptor signaling is not clear. In this study, we show that Tec protein is expressed at substantially lower levels in primary T and B cells relative to Itk and Btk, respectively. However, Tec is up-regulated upon T-cell activation and in Th1 and Th2 cells. In functional experiments that mimic Tec up-regulation, we find that Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase Cγ (PLC-γ) phosphorylation and NFAT (nuclear factor of activated T cells) activation. In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation. Tec-induced NFAT activation requires PLC-γ, but not the adapters LAT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-γ. Finally, we show that the unique effector function for Tec correlates with a unique subcellular localization. We hypothesize that Tec functions in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors.

scholarly journals Functional Ambivalence of Dendritic Cells: Tolerogenicity and Immunogenicity

2021 ◽  
Vol 22 (9) ◽  
pp. 4430
Author(s):  
Ji-Hee Nam ◽  
Jun-Ho Lee ◽  
So-Yeon Choi ◽  
Nam-Chul Jung ◽  
Jie-Young Song ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Inflammatory Diseases ◽  
Immunosuppressive Agents ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Cell Mediated Immunity ◽  
Antigen Presenting

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the method of induction and/or the presence of immunosuppressive agents. Tolerogenic dendritic cells (tDCs) induce immune tolerance by activating CD4+CD25+Foxp3+ regulatory T (Treg) cells and/or by producing cytokines that inhibit T cell activation. These findings suggest that tDCs may be an effective treatment for autoimmune diseases, inflammatory diseases, and infertility.

7.2-02 Flow cytometric analysis of T cell activation antigens

1989 ◽  
Vol 26 ◽  
pp. 64
Author(s):  
B.K Book ◽  
A.F Chai ◽  
R.A Sidner ◽  
S.B Leapman ◽  
R.S Filo
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Flow Cytometric Analysis ◽  
Flow Cytometric ◽  
Activation Antigens

scholarly journals Flow cytometric analysis of the binding of eleven lectins to human T- and B-cells and to human T- and B-cell lines

Cytometry ◽  
1984 ◽  
Vol 5 (2) ◽  
pp. 204-209 ◽  
Author(s):  
Jeannette Malin-Berdel ◽  
Günther Valet ◽  
Eckhart Thiel ◽  
John Anthony Forrester ◽  
Lutz Gürtler
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Flow Cytometric Analysis ◽  
T And B Cells ◽  
Flow Cytometric

scholarly journals Changes in epigenetic profiles throughout early childhood and their relationship to the response to pneumococcal vaccination

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sara Pischedda ◽  
Daniel O’Connor ◽  
Benjamin P. Fairfax ◽  
Antonio Salas ◽  
Federico Martinon-Torres ◽  
...  
Keyword(s):  
Early Childhood ◽  
Immune System ◽  
T Cell Activation ◽  
Specific Antibody ◽  
Cell Activation ◽  
Pneumococcal Vaccination ◽  
Antibody Responses ◽  
Healthy Children ◽  
Epigenetic Changes ◽  
Pneumococcal Infections

Abstract Background Pneumococcal infections are a major cause of morbidity and mortality in young children and immaturity of the immune system partly underlies poor vaccine responses seen in the young. Emerging evidence suggests a key role for epigenetics in the maturation and regulation of the immune system in health and disease. The study aimed to investigate epigenetic changes in early life and to understand the relationship between the epigenome and antigen-specific antibody responses to pneumococcal vaccination. Methods The epigenetic profiles from 24 healthy children were analyzed at 12 months prior to a booster dose of the 13-valent pneumococcal conjugate vaccine (PCV-13), and at 24 months of age, using the Illumina Methylation 450 K assay and assessed for differences over time and between high and low vaccine responders. Results Our analysis revealed 721 significantly differentially methylated positions between 12 and 24 months (FDR < 0.01), with significant enrichment in pathways involved in the regulation of cell–cell adhesion and T cell activation. Comparing high and low vaccine responders, we identified differentially methylated CpG sites (P value < 0.01) associated with HLA-DPB1 and IL6. Conclusion These data imply that epigenetic changes that occur during early childhood may be associated with antigen-specific antibody responses to pneumococcal vaccines.

scholarly journals Vitamin D Supplementation Modulates T Cell–Mediated Immunity in Humans: Results from a Randomized Control Trial

2016 ◽  
Vol 101 (2) ◽  
pp. 533-538 ◽  
Author(s):  
Gauree Gupta Konijeti ◽  
Pankaj Arora ◽  
Matthew R. Boylan ◽  
Yanna Song ◽  
Shi Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cell ◽  
Vitamin D Deficiency ◽  
T Cell Activation ◽  
Vitamin D3 ◽  
Cell Activation ◽  
Atp Release ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Ancillary Study

Abstract Context: Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse. Objective: Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency. Design: This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial. Setting: This study was undertaken in a single academic medical center. Participants: Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included. Intervention: In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up. Main Outcome Measure: Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure. Results: Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, −219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, −69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06–1.11). Conclusions: In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.

scholarly journals PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaitao Li ◽  
Zhou Yuan ◽  
Jintian Lyu ◽  
Eunseon Ahn ◽  
Simon J. Davis ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Clinical Success ◽  
Clinical Intervention ◽  
Cell Receptor ◽  
Cell Interaction ◽  
Antigen Recognition ◽  
Inhibitory Function ◽  
Src Homology

AbstractDespite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1’s targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR–pMHC–CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1’s potent inhibitory function and its value as a target for clinical intervention.

Sign in / Sign up

Export Citation Format

Share Document