Untired Regulatory T Cells: Untying Fatigue from T Cell Regulation in Multiple Sclerosis

2009 ◽  
Vol 62 (6) ◽  
pp. 327-329
Author(s):  
Harald H. Hofstetter ◽  
Vsevolod Smolianov ◽  
Hans-Peter Hartung
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Regulation ◽  
T Cell Regulation

scholarly journals T cell regulation of autoimmune interstitial nephritis.

1990 ◽  
Vol 1 (2) ◽  
pp. 140-149
Author(s):  
C J Kelly
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Interstitial Nephritis ◽  
Host Susceptibility ◽  
Therapeutic Modality ◽  
Cell Regulation ◽  
Organ Specific ◽  
T Cell Regulation

Research in organ-specific autoimmunity has been greatly facilitated over the past decade by advances in cellular and molecular immunology. Such studies have greatly expanded our understanding of autoimmune effector mechanisms and the nature of the target antigens recognized by these mediators. Another facet of organ-specific autoimmunity concerns the definition of those factors that determine host susceptibility to disease. This review outlines studies performed in two models of autoimmune interstitial nephritis that focus on issues of susceptibility and tolerance to parenchymal self antigens. In both models, antigen-specific regulatory T cells modulate the effector limb of the nephritogenic immune response and the pattern of interstitial injury. This modulation can be either stimulatory or inhibitory. The dominant regulatory effect is linked to genes in the major histocompatibility locus and is tightly correlated with disease expression. Regulatory T cells which inhibit the nephritogenic immune response can also be cultured in vitro and are highly efficacious as a therapeutic modality. These studies provide both the background and requisite reagents for delineating the mechanism(s) underlying antigen-specific T cell regulation.

scholarly journals Mononuclear phagocytes drive Mertk-dependent T cell regulation at autoimmune and tumor sites

2019 ◽  
Author(s):  
Robin S. Lindsay ◽  
Kristen E. Dew ◽  
Erika Rodriguez ◽  
Jennifer C. Whitesell ◽  
Dayna Tracy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Phagocytes ◽  
Diabetic Patients ◽  
Cell Regulation ◽  
Peripheral Tissues ◽  
Disease Site ◽  
T Cell Regulation ◽  
Cell Arrest

AbstractUnderstanding mechanisms of immune regulation is key to developing effective immunotherapies for autoimmunity and cancer; however, many regulatory mechanisms have not been elucidated. By analyzing T cell motility and activation at the disease site as well as disease progression, we examined the role of mononuclear phagocytes in driving regulation of effector T cells in type 1 diabetes and melanoma. We report that mononuclear phagocytes in the islets impair T cell responsiveness to antigen by preventing antigen-mediated T cell arrest. Mononuclear phagocytes in the autoimmune lesion express the TAM family receptor tyrosine kinase Mertk which functions in efferocytosis. Inhibition or deficiency of Mertk led to a release from T cell regulation characterized by enhanced T cell arrest in pre-diabetic islets and at the tumor site. This T cell arrest was accompanied by increased T cell-antigen presenting cell interactions as well as increased antigen experience and effector function by T cells in the islets. Notably, the effect of Mertk inhibition on T cell regulation was only seen at the disease site in the islets, not in draining lymph nodes. Inhibition of Mertk-dependent T cell regulation culminated in the rapid acceleration of autoimmune pathology and disease. In human islets, the number of Mertk-expressing cells were increased in remaining insulin-containing islets from type 1 diabetic patients, suggesting that they might have a protective role in human disease. These data indicate that Mertk signaling in mononuclear phagocytes drives T cell regulation that functions specifically at the disease site in peripheral tissues through a mechanism that prevents T cell arrest and response to antigen.

scholarly journals Platelet Induced Functional Alteration of CD4+ and CD8+ T Cells in HNSCC

2020 ◽  
Vol 21 (20) ◽  
pp. 7507
Author(s):  
Christina Polasky ◽  
Franziska Wendt ◽  
Ralph Pries ◽  
Barbara Wollenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Spatial Separation ◽  
Cell Regulation ◽  
Activation Markers ◽  
Indirect Contact ◽  
Cell Functions ◽  
T Cell Regulation ◽  
Regulatory Functions

Platelets (PLT) are the second most abundant cell type in human blood and exert various immune-regulatory functions under both physiological and pathological conditions. In fact, immune cell regulation via platelets has been demonstrated in several studies within the past decade. However, the exact mechanisms behind T cell regulation remain poorly understood. We questioned whether the formation of aggregates of platelets and T cells has an impact on T-cell functions. In the present study, we stimulated PBMC cultures with anti-CD3 and anti-CD28 mABs and cultured them at a PLT: PBMC ratio of 1:1 or 100:1. After 24, 48, and 72 h, PD-1, PD-L1 expression, and proliferation were analyzed on T cells using flow cytometry. Cytokine production was measured in PHA stimulated CD4 cells after 6 h. We found a significant platelet-mediated decrease in PD-1 and PD-L1 expression, proliferation, as well as IFN-γ and TNF-α production. Perturbations also at least partially remained after spatial separation of PLTs from PBMCs in Transwell-assays. T cell-platelet aggregates showed similar levels of activation markers, proliferation, and secreted cytokines as their non-complexed counterparts. Results indicate a platelet mediated regulation of T cells via direct and indirect contact, but only mediocre effects of the complex formation itself.

Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy

2011 ◽  
Vol 18 (6) ◽  
pp. 788-798 ◽  
Author(s):  
M Chiarini ◽  
F Serana ◽  
C Zanotti ◽  
R Capra ◽  
S Rasia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Interferon Beta ◽  
Central Memory ◽  
T Cell Subsets ◽  
Individual Treatment ◽  
Cell Phenotype ◽  
Multiple Sclerosis Patients

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

scholarly journals Fine-Tuning of Regulatory T Cell Function: The Role of Calcium Signals and Naive Regulatory T Cells for Regulatory T Cell Deficiency in Multiple Sclerosis

2013 ◽  
Vol 190 (10) ◽  
pp. 4965-4970 ◽  
Author(s):  
Alexander Schwarz ◽  
Marijana Schumacher ◽  
Daniel Pfaff ◽  
Kai Schumacher ◽  
Sven Jarius ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Cell Function ◽  
Fine Tuning ◽  
Calcium Signals ◽  
T Cell Function
Sign in / Sign up

Export Citation Format

Share Document