scholarly journals FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients

2015 ◽  
Vol 6 (5) ◽  
pp. e1741-e1741 ◽  
Author(s):  
M T Cencioni ◽  
S Santini ◽  
G Ruocco ◽  
G Borsellino ◽  
M De Bardi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cell Death ◽  
Autoimmune Diseases ◽  
Fas Ligand ◽  
Th1 Cells ◽  
T Helper ◽  
Th Cells ◽  
Activation Induced Cell Death ◽  
Healthy Donors ◽  
Multiple Sclerosis Patients

Abstract Functionally distinct T-helper (Th) subsets orchestrate immune responses. Maintenance of homeostasis through the tight control of inflammatory Th cells is crucial to avoid autoimmune inflammation. Activation-Induced Cell Death (AICD) regulates homeostasis of T cells, and it has never been investigated in human Th cells. We generated stable clones of inflammatory Th subsets involved in autoimmune diseases, such as Th1, Th17 and Th1/17 cells, from healthy donors (HD) and multiple sclerosis (MS) patients and we measured AICD. We find that human Th1 cells are sensitive, whereas Th17 and Th1/17 are resistant, to AICD. In particular, Th1 cells express high level of FAS-ligand (FASL), which interacts with FAS and leads to caspases’ cleavage and ultimately to cell death. In contrast, low FASL expression in Th17 and Th1/17 cells blunts caspase 8 activation and thus reduces cell death. Interestingly, Th cells obtained from healthy individuals and MS patients behave similarly, suggesting that this mechanism could explain the persistence of inflammatory IL-17-producing cells in autoimmune diseases, such as MS, where their generation is particularly substantial.

Activation-induced cell death in T lymphocytes from multiple sclerosis patients

2014 ◽  
Vol 272 (1-2) ◽  
pp. 51-55 ◽  
Author(s):  
Montserrat Moreno ◽  
Laura Negrotto ◽  
Jordi Río ◽  
Rana Moubarak ◽  
Isabel Martín ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cell Death ◽  
T Lymphocytes ◽  
Activation Induced Cell Death ◽  
Multiple Sclerosis Patients

scholarly journals Distinct Expression of Inflammatory Features in T Helper 17 Cells from Multiple Sclerosis Patients

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 533 ◽  
Author(s):  
Alessia Capone ◽  
Manuela Bianco ◽  
Gabriella Ruocco ◽  
Marco De Bardi ◽  
Luca Battistini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Chronic Inflammatory Disease ◽  
T Helper ◽  
T Helper 17 ◽  
Inflammatory Status ◽  
Healthy Donors ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T helper (Th) 17 lymphocytes play a role in the pathogenesis of MS. Indeed, Th17 cells are abundant in the cerebrospinal fluid and peripheral blood of MS patients and promote pathogenesis in the mouse model of MS. To gain insight into the function of Th17 cells in MS, we tested whether Th17 cells polarized from naïve CD4 T cells of healthy donors and MS patients display different features. To this end, we analysed several parameters that typify the Th17 profile during the differentiation process of naïve CD4 T cells obtained from relapsing-remitting (RR)-MS patients (n = 31) and healthy donors (HD) (n = 28). Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells. Interestingly, IL-1R1 expression is also increased in Th17 cells circulating in the blood of MS patients compared to healthy donors. Since IL-2, IL-21, TNF-β, and IL-1R1 play a crucial role in the activation of immune cells, our data indicate that high expression of these molecules in Th17 cells from MS patients could be related to their high inflammatory status.

scholarly journals Inherent low Erk and p38 activity reduce Fas Ligand expression and degranulation in T helper 17 cells leading to activation induced cell death resistance

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 54339-54359 ◽  
Author(s):  
Doureradjou Peroumal ◽  
Thiruvaimozhi Abimannan ◽  
Ravichandra Tagirasa ◽  
Jyothi Ranjan Parida ◽  
Santosh Kumar Singh ◽  
...  
Keyword(s):  
Cell Death ◽  
Fas Ligand ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cells ◽  
Activation Induced Cell Death ◽  
Ligand Expression

scholarly journals Antibodies from the Sera of Multiple Sclerosis Patients Efficiently Hydrolyze Five Histones

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 741 ◽  
Author(s):  
Baranova ◽  
Mikheeva ◽  
Buneva ◽  
Nevinsky
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Progressive Multiple Sclerosis ◽  
Significant Inhibition ◽  
Healthy Donors ◽  
Negative Role ◽  
Average Activity ◽  
Multiple Sclerosis Patients ◽  
Toxic Reactions

It is known that intranuclear histones can be pernicious after entering to the extracellular space. In addition, the immunization of animals with exogenous histones leads to systemic inflammatory and toxic reactions. Abzymes—autoantibodies with enzymatic activities—are the distinctive feature of autoimmune diseases and they can be especially dangerous to humans. Here, electrophoretically homogeneous IgGs were isolated from sera of patients with multiple sclerosis (MS) by chromatography on several affinity sorbents. We present evidence that sera of all MS patients contain autoantibodies against histones and 73% of IgGs purified from the sera of 59 MS patients efficiently hydrolyze from one to five histones: H1, H2a, H2b, H3, and H4. The relative average efficiency of the histones hydrolysis was ~3.9-fold higher than that for healthy donors. The relative average activity of IgGs depends on the type of MS and decreased approximately in the following order: debut of MS, secondary progressive multiple sclerosis, remitting multiple sclerosis, remittent progressive multiple sclerosis. Similar to proteolytic abzymes of patients with several autoimmune diseases, histone-hydrolyzing IgGs from MS patients were inhibited in the presence of specific inhibitors of serine and of metal-dependent proteases, but an unexpected significant inhibition of the activity by inhibitors of thiol-like and especially acidic proteases was observed. Since IgGs can efficiently hydrolyze histones, a negative role of abzymes in the development of MS cannot be excluded.

scholarly journals Fas ligand mediates activation-induced cell death in human T lymphocytes.

1995 ◽  
Vol 181 (1) ◽  
pp. 71-77 ◽  
Author(s):  
M R Alderson ◽  
T W Tough ◽  
T Davis-Smith ◽  
S Braddy ◽  
B Falk ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Fas Ligand ◽  
Significant Proportion ◽  
Cell Receptor ◽  
Target Cells ◽  
Activated T Cells ◽  
Activation Induced Cell Death ◽  
Fas L

A significant proportion of previously activated human T cells undergo apoptosis when triggered through the CD3/T cell receptor complex, a process termed activation-induced cell death (AICD). Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in cytolysis. We demonstrate that these two pathways of apoptosis are causally related. Stimulation of previously activated T cells resulted in the expression of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell lines. The data indicate AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions.

Interferon-β1b augments activation-induced T-cell death in multiple sclerosis patients

The Lancet ◽  
1999 ◽  
Vol 353 (9162) ◽  
pp. 1413-1414 ◽  
Author(s):  
Arthur Kaser ◽  
Florian Deisenhammer ◽  
Thomas Berger ◽  
Herbert Tilg
Keyword(s):  
Multiple Sclerosis ◽  
Cell Death ◽  
T Cell ◽  
Multiple Sclerosis Patients

scholarly journals Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis

2019 ◽  
Vol 20 (18) ◽  
pp. 4323 ◽  
Author(s):  
Salvo Danilo Lombardo ◽  
Emanuela Mazzon ◽  
Maria Sofia Basile ◽  
Giorgia Campo ◽  
Federica Corsico ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Metastasis ◽  
Treg Cells ◽  
T Helper ◽  
Autoimmune Encephalomyelitis ◽  
Healthy Donors

Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell–cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that TSPAN32 is expressed at higher levels in the lymphoid lineage as compared to myeloid cells. In vitro activation of T helper cells via anti-CD3/CD28 is associated with a significant downregulation of TSPAN32. Interestingly, engagement of CD3 is sufficient to modulate TSPAN32 expression, and its effect is potentiated by costimulation with anti-CD28, but not anti-CTLA4, -ICOS nor -PD1. Accordingly, we measured the transcriptomic levels of TSPAN32 in polarized T cells under Th1 and Th2 conditions and TSPAN32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, TSPAN32 underwent minor changes upon activation. The in vitro data were finally translated into the context of multiple sclerosis (MS). Encephalitogenic T cells from Myelin Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis (EAE) mice showed significantly lower levels of TSPAN32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of TSPAN32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for TSPAN32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases.

scholarly journals Mast Cells Stimulated with Peptidoglycan from Staphylococcus aureus Augment the Development of Th1 Cells

2018 ◽  
Vol 21 ◽  
pp. 296-304
Author(s):  
Katsuhiko Matsui ◽  
Saeko Kanai ◽  
Manami Ikuta ◽  
Saki Horikawa
Keyword(s):  
Staphylococcus Aureus ◽  
Mast Cells ◽  
Chronic Inflammation ◽  
Cell Development ◽  
Th1 Cells ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th2 Cell ◽  
Helper Type

Background: The skin of patients with atopic dermatitis (AD) is superficially colonized by Staphylococcus aureus. We have previously found that percutaneous permeation of peptidoglycan (PEG) from S. aureus increases the number of mast cells in the dermis, as seen in skin lesions of AD patients. The purpose of the present study was to clarify the influence of PEG on T helper type 1 (Th1)/ T helper type 2 (Th2) cell development mediated by mast cells. Methods: Mast cells were induced by long-term culture of murine spleen cells in medium supplemented with tumor necrosis factor (TNF)- a. Ovalbumin (OVA) peptide-pulsed mast cells were incubated with naïve Th cells in the presence or absence of PEG. Five days later, Th cells in the culture were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and Th1/Th2 cytokine production was investigated by enzyme-linked immunosorbent assay. Results: It was confirmed that the mast cells we obtained had surface expression of I-Ad, worked as antigen-presenting cells, and induced Th1 cell and Th2 cell development. The stimulation of mast cells with PEG enhanced the development of Th1 cells but not that of Th2 cells. The increase of Th1 cell development stimulated by PEG was associated with an increase in the expression of Notch ligand Delta 1 in the mast cells. Furthermore, treatment of mast cells with the macrolide antibiotic josamycin suppressed Th1 cell development and this was correlated with a reduction of both Delta 1 expression and interleukin (IL)-12 production in mast cells. Conclusions: Colonization of S. aureus on the lesioned skin of AD patients contributes to not only an increase in the number of mast cells but also Th1 cell development mediated by mast cells in the dermis and subsequent induction of chronic inflammation, which is characterized by up-regulation of the Th1 cytokine, interferon (IFN)- g. Therefore, application of josamycin to the lesional skin of AD patients may provide relief from chronic inflammation mediated by mast cells.

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