Long life span of tolerant T cells and the role of antigen in maintenance of peripheral tolerance

1995 ◽  
Vol 7 (2) ◽  
pp. 331-336 ◽  
Author(s):  
Judith Alferink ◽  
Birgit Schittek ◽  
Günter Schönrich ◽  
Günter J. Hämmerling ◽  
Bernd Arnold
Keyword(s):  
T Cells ◽  
Life Span ◽  
Peripheral Tolerance ◽  
Long Life

scholarly journals Potential Role of Trace Elements (Al, Cu, Zn, and Se) in Multiple Sclerosis Physiopathology

2020 ◽  
Vol 27 (4) ◽  
pp. 163-177
Author(s):  
Mohammad Sadegh Hesamian ◽  
Nahid Eskandari
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Trace Elements ◽  
Plasma Cells ◽  
Peripheral Tolerance ◽  
The Central Nervous System ◽  
Living Organisms ◽  
Tolerance Breakdown ◽  
Peripheral Immune Cells

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body’s functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.

scholarly journals Memory T cells are anergic to the superantigen staphylococcal enterotoxin B.

1992 ◽  
Vol 176 (2) ◽  
pp. 575-579 ◽  
Author(s):  
W T Lee ◽  
E S Vitetta
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Staphylococcal Enterotoxin ◽  
Peripheral Tolerance ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B

We have used staphylococcal enterotoxin B (SEB) to study the role of naive and memory T cells in the induction of peripheral tolerance. After administration of SEB to mice, the numbers of naive and memory T cells increase, as does the proportion of memory T cells, which are unresponsive to further stimulation with SEB in vitro. In addition, memory T cells generated in response to conventional antigen, which proliferate and provide help to B cells in the presence of the conventional antigen, fail to respond to superantigen. Hence, memory T cells, in general, are anergized by SEB. These results suggest that SEB-induced activation and anergy reflect the combined responses of naive and memory T cells. The differential activation vs. anergy of naive and memory T cells by superantigen may be related to cytokine production and may play an important role in the etiology of autoimmune diseases or immunodeficiency diseases such as acquired immune deficiency syndrome.

scholarly journals Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens

2021 ◽  
Vol 12 ◽  
Author(s):  
Giovanna Flores-Mendoza ◽  
Noé Rodríguez-Rodríguez ◽  
Rosa M. Rubio ◽  
Iris K. Madera-Salcedo ◽  
Florencia Rosetti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Peripheral Tolerance ◽  
Tolerance Mechanism ◽  
Genetic Deficiency ◽  
Self Antigen ◽  
Insight Into ◽  
Self Antigens

Activation of self-reactive CD8+ T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of Fas and Fasl causes the accumulation of double-negative (DN; CD3+ TCR-αβ+ CD4- CD8-) T cells that have been proposed to derive from CD8+ cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and FasL induction by different stimuli and analyzed the effects of Fas/FasL deficiency during a protective immune response and after exposure to self-antigens. Our data describes how Fas and FasL upregulation differs depending on the setting of CD8 T cell activation and demonstrates that Fas/FasL signaling maintains CD8 expression during repetitive antigen stimulation and following self-antigen encounter. Together, our results reveal an unexpected role of Fas/FasL signaling and offer a new insight into the role of these molecules in the regulation of immune tolerance.

scholarly journals Role of regulatory T cells in experimental autoimmune glomerulonephritis

2019 ◽  
Vol 316 (3) ◽  
pp. F572-F581 ◽  
Author(s):  
Stefanie Klinge ◽  
Karsten Yan ◽  
Daniel Reimers ◽  
Karen-Maria Brede ◽  
Joanna Schmid ◽  
...  
Keyword(s):  
T Cells ◽  
Crescentic Glomerulonephritis ◽  
Treg Cells ◽  
Peripheral Tolerance ◽  
Rapid Loss ◽  
Type Iv ◽  
Forkhead Box ◽  
Goodpasture Antigen ◽  
Experimental Autoimmune

Anti-glomerular basement membrane (anti-GBM) disease is characterized by antibodies and T cells directed against the Goodpasture antigen, the noncollagenous domain of the α3-chain of type IV collagen [α3(IV)NC1] of the GBM. Consequences are the deposition of autoantibodies along the GBM and the development of crescentic glomerulonephritis (GN) with rapid loss of renal function. Forkhead box protein P3 (Foxp3)+ regulatory T (Treg) cells are crucial for the maintenance of peripheral tolerance to self-antigens and the prevention of immunopathology. Here, we use the mouse model of experimental autoimmune GN to characterize the role of Treg cells in anti-GBM disease. Immunization of DBA/1 mice with α3(IV)NC1 induced the formation of α3(IV)NC1-specific T cells and antibodies and, after 8–10 wk, the development of crescentic GN. Immunization resulted in increased frequencies of peripheral Treg cells and renal accumulation of these cells in the stage of acute GN. Depletion of Treg cells during immunization led to enhanced generation of α3(IV)NC1-specific antibodies and T cells and to aggravated GN. In contrast, depletion or expansion of the Treg cell population in mice with established autoimmunity had only minor consequences for renal inflammation and did not alter the severity of GN. In conclusion, our results indicate that in anti-GBM disease, Treg cells restrict the induction of autoimmunity against α3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has been established.

Double Negative T Cells Influence TCR VB Variablity to Induce Allotolerance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 759-759
Author(s):  
Zachariah A. McIver ◽  
Marcin Wlodarski ◽  
Jennifer Powers ◽  
Christine O’Keefe ◽  
Tao Jin ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Peripheral Tolerance ◽  
Double Negative ◽  
Clonal Deletion ◽  
Tcr Repertoire ◽  
Double Negative T Cells

Abstract Immune alloresponsiveness following allogeneic HSCT is influenced by the dynamics of immune reconstitution and development of allotolerance. In general, tolerance is induced by thymic clonal deletion (central) and apoptosis or suppression of alloresponsive lymphocytes by regulatory T cells in the periphery. We have recently demonstrated that the size of the TCR repertoire within the CD4 and CD8 compartments can be assessed using VB spectrum by flow cytometry, and expansions/losses of individual TCR VB families can be used as a surrogate marker of TCR variability. (Exp. Hem.32: 1010–1022; Br. J. Haematol.129:411–419). Additionally, regulatory T cells can also impact the clonal contractions and expansions within the TCR VB repertoire. Various types of regulatory T cells have been described including CD4+CD25+, CD8+, NK T−cells, and CD3+CD4/CD8− double negative T cells (DN Tregs). In our current study we investigated the role of DN Tregs on the restoration of immune repertoire diversity. We hypothesized that alloresponsiveness clinically detected as a manifestation of GvHD may be associated with oligoclonal T−cell expansions, and in this context decreased numbers of regulatory T cells suggest deficient tolerizing function by regulatory T cells including DN Tregs. Here we studied a cohort of 60 HSCT recipients (AML, CML, CLL, NHL, AA, and PV), of which 25 patients received matched unrelated donor grafts and 35 received matched sibling donor grafts. Blood was sampled between 2003–2006 at monthly intervals after HSCT, and flow cytometry for TCR repertoire in CD4 and CD8 cells as well as the numbers of DN cells were recorded. Additionally, separate samples were collected for measurement of chimerism and were included in analysis when donor lymphoid chimerism was > 60%. A subset analysis was performed based on the presence/absence of GvHD. For the 27/60 (45%) patients with episodes of GvHD, results were obtained at the time of diagnosis of GvHD (grade > 2), while for patients in whom notable GvHD was not captured, the steady−state values at corresponding times were used for analysis. For all patients serial evaluations were available. For the purpose of this study, significant VB expansions/contractions were defined as +/− 2 standard deviation over the average VB family size. Using Cox proportional hazards analysis to identify univariate risk factors for GVHD, CD8 VB TCR contractions > 14 VB families (58.3% contraction of entire CD4 VB repertoire) constituted a strong indicator for increased risk (HR=7.61, p=0.011). This observation is consistent with the fact that oligoclonality of alloreactive T cell clones is frequently accompanied by a significant contraction/loss of remaining VB families and may herald heightened alloresponsiveness as a manifestation of GvHD. Estimation for correlation by Pearson’s correlation coefficient also demonstrated that percentage of DN cells strongly correlated with a normalization of CD4 VB TCR repertoire (lower number of expansions; N=57, R= −0.51, p=0.027), supporting our hypothesis that DN cells participate in peripheral tolerance and suppress proliferative, alloresponsive CD4 clones. In summary, our results further characterize TCR variability post HSCT and define the role of DN cells in the induction of allotolerance.

PIR-B expressing CD8+ T cells exhibit features of Tc1 and Tc17 in SKG mice

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2325-2329 ◽  
Author(s):  
Kathrin Rothe ◽  
Dagmar Quandt ◽  
Gabriele Köhler ◽  
Simon Jasinski-Bergner ◽  
Barbara Seliger ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Clinical Symptoms ◽  
Ex Vivo ◽  
Peripheral Tolerance ◽  
Autoimmune Arthritis ◽  
Specific Pathogen ◽  
Inflammatory Phenotype

Abstract Objective In autoimmune arthritis, TCR signalling is attenuated by peripheral tolerance mechanisms. We have described previously a population of inhibitory receptor LIR-1 expressing autoreactive CD8+ T cells in rheumatoid arthritis. Here, we investigated the role of CD8+ T cells in murine autoimmune arthritis by analysing their expression of the mouse orthologue of LIR-1, PIR-B. Methods Frequencies of PIR-B+CD8+ T cells were determined in the SKG arthritis model. The phenotype of those cells was determined ex vivo by FACS and functionality was investigated by means of cytokine production and cytolytic potential upon activation in vitro. Results SKG mice, under non-SPF (specific pathogen-free) conditions with clinical symptoms of arthritis, were found to harbour significantly increased frequencies of PIR-B+CD8+ T cells. Those cells showed a pro-inflammatory phenotype with preferential production of IL-17 and IFN-γ. The frequency of those cells correlated inversely with the arthritis score, indicating that they might represent autoreactive, but functionally inhibited, CD8+ T cells. Conclusion PIR-B+CD8+ T cells from SKG mice show a cytotoxic and pro-inflammatory phenotype. Inhibition of CD8+ T cell autoreactivity by PIR-B/LIR-1 receptor signalling might be a counter-regulatory mechanism to curb autoreactivity and arthritis.

scholarly journals Regulatory Role of CD4+ T Cells in Myocarditis

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Daria Vdovenko ◽  
Urs Eriksson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Young Patients ◽  
Peripheral Tolerance ◽  
T Cell Subsets ◽  
High Plasticity ◽  
Clonal Deletion ◽  
Effector T Cell

Myocarditis is an important cause of heart failure in young patients. Autoreactive, most often, infection-triggered CD4+ T cells were confirmed to be critical for myocarditis induction. Due to a defect in clonal deletion of heart-reactive CD4+ T cells in the thymus of mice and humans, significant numbers of heart-specific autoreactive CD4+ T cells circulate in the blood. Normally, regulatory T cells maintain peripheral tolerance and prevent spontaneous myocarditis development. In the presence of tissue damage and innate immune activation, however, activated self-antigen-loaded dendritic cells promote CD4+ effector T cell expansion and myocarditis. So far, a direct pathogenic role has been described for both activated Th17 and Th1 effector CD4+ T cell subsets, though Th1 effector T cell-derived interferon-gamma was shown to limit myocarditis severity and prevent transition to inflammatory dilated cardiomyopathy. Interestingly, recent observations point out that various CD4+ T cell subsets demonstrate high plasticity in maintaining immune homeostasis and modulating disease phenotypes in myocarditis. These subsets include Th1 and Th17 effector cells and regulatory T cells, despite the fact that there are still sparse and controversial data on the specific role of FOXP3-expressing Treg in myocarditis. Understanding the specific roles of these T cell populations at different stages of the disease progression might provide a key for the development of successful therapeutic strategies.

scholarly journals Suppressor T Cells in Human Diseases

2004 ◽  
Vol 200 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Clare Baecher-Allan ◽  
David A. Hafler
Keyword(s):  
T Cells ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Peripheral Tolerance ◽  
Human Diseases ◽  
Suppressor T Cells ◽  
Wide Range ◽  
Human Immune

Although central and peripheral tolerance are important for the regulation of human immune responses to self- and microbial antigens, an important role of suppressor CD4+ CD25+ T cells is suggested from the recent investigations of human autoimmune diseases and HIV. These new data provide increasing evidence that altered function of CD4+ CD25+ T cells may be an important factor in a wide range of human inflammatory and infectious diseases.

scholarly journals Regulatory T cells in acute and chronic kidney diseases

2018 ◽  
Vol 314 (5) ◽  
pp. F679-F698 ◽  
Author(s):  
Rahul Sharma ◽  
Gilbert R. Kinsey
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Peripheral Tolerance ◽  
Autoimmune And Inflammatory Diseases

Foxp3-expressing CD4+ regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.

Deciphering the role of TRIB1 in regulatory T-cells

2015 ◽  
Vol 43 (5) ◽  
pp. 1075-1078 ◽  
Author(s):  
Richard Danger ◽  
Emilie Dugast ◽  
Faouzi Braza ◽  
Sophie Conchon ◽  
Sophie Brouard
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Peripheral Tolerance ◽  
Antibody Mediated Rejection ◽  
Screening Experiments ◽  
Cluster Of Differentiation

The role of regulatory T-cells (Tregs) is crucial to maintain immune homoeostasis by controlling peripheral tolerance. A better understanding in the molecular mechanisms involved in the biology of these Tregs could improve their expansion and selection to treat immune-related diseases, achieve immunosuppression-free organ transplantation and to specifically target them in cancer. We reported on the overexpression of tribbles-1 (TRIB1) in Tregs compared with their counterpart naive T-cells and that TRIB1 interacts with the master molecule of Tregs, forkhead box P3 (FOXP3), a transcription factor essential for Treg suppressive activity. We demonstrated that these two molecules interact together in the nucleus of Tregs and TRIB1 overexpression is associated with a decrease in their proliferative capacities. Since TRIB1 was reported to be overexpressed in the blood of renal transplanted patients with chronic antibody-mediated rejection (CAMR), altogether, these results suggest TRIB1 could be linked to the decrease proportion of Tregs in patients exhibiting CAMR and a key player in Tregs through its FOXP3 interaction. In addition, yeast two-hybrid screening experiments highlighted that TRIB1 potentially interacts with molecules playing roles in intracellular events following T-cell activation and particularly cluster of differentiation (CD)4+ T-cells. This suggests still non explored potential links between TRIB1 in Tregs. Our goal is thus to decipher the role of TRIB1 in the Treg biology, notably in pathways known to involved its partner and main transcriptional factor of Tregs, FOXP3 and to determine the role of TRIB1 in immune pathologies.

Sign in / Sign up

Export Citation Format

Share Document