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

Arroyo, María Perla Moreno; Negrotto, Laura; Río, Jordi; Moubarak, Rana S.; Martín, Isabel Rodríguez; Bustamante, Marta F.; Comella, Joan X.; Vidal-Jordana, Ángela; Pérez-Boza, Jennifer; Montalbán, Xavier; Comabella, Manuel

doi:10.1016/j.jneuroim.2014.04.007

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…As previously discussed, survivin is endowed with a regulative role in immune responses, implying that it may have a role in developing autoreactive immune responses in MS patients. Several studies have indicated that AICD in T cell subsets from MS patients is defective ( 117 ). In this context, analyses of T cells from MS patients outlined that these cells had an enhanced level of anti-apoptotic survivin, which contributes to the disease’s progression ( 54 , 118 , 119 ).…”

Section: Irregular Expression Of Survivin-specific Micrornas In Speci...mentioning

confidence: 99%

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

et al. 2022

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It has been well established that the etiopathogenesis of diverse autoimmune diseases is rooted in the autoreactive immune cells’ excessively proliferative state and impaired apoptotic machinery. Survivin is an anti-apoptotic and mitotic factor that has sparked a considerable research interest in this field. Survivin overexpression has been shown to contribute significantly to the development of autoimmune diseases via autoreactive immune cell overproliferation and apoptotic dysregulation. Several microRNAs (miRNAs/miRs) have been discovered to be involved in survivin regulation, rendering the survivin-miRNA axis a perspective target for autoimmune disease therapy. In this review, we discuss the role of survivin as an immune regulator and a highly implicated protein in the pathogenesis of autoimmune diseases, the significance of survivin-targeting miRNAs in autoimmunity, and the feasibility of targeting the survivin-miRNA axis as a promising therapeutic option for autoimmune diseases.

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Section: Irregular Expression Of Survivin-specific Micrornas In Speci...mentioning

confidence: 99%

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

et al. 2022

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“…p53 also reduces autoimmunity by influencing the differentiation of T cells through repression of STAT3 mediated differentiation of Th17 cells in favor of promoting T regulatory cells (31). Conversely, loss of p53 expression or function exaggerates autoimmunity and co-associates with many autoimmune conditions where defective AICD is also problematic, including arthritis (32–36), multiple sclerosis, (37,38), and Crohn's disease (39,40). Our data suggest that activation of p53 plays a critical role in T cell death and offers a potential explanation for the co-association between p53 and autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Adoptive T-cell Therapy Is Improved by Treatment with the Antioxidant N-Acetyl Cysteine, Which Limits Activation-Induced T-cell Death

et al. 2016

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While adoptive transfer of autologous tumor antigen-specific T cell immunotherapy can produce remarkable clinical efficacy, most patients do not achieve durable complete responses. We hypothesized that reducing susceptibility of T cells to activation-induced cell death (AICD), which increases during the rapid in vitro expansion of therapeutic T cells before their infusion, might improve the persistence of adoptively transferred cells. Our investigations revealed that repetitive stimulation of the T cell receptor (TCR) induced AICD, as a result of activating the DNA damage response pathway through ATM-mediated Ser15 phosphorylation of p53. Activation of this DNA damage response pathway also occurred upon antigen-specific restimulation in TCR-transduced TIL1383I T cells prepared for adoptive transfer to patients as part of a clinical trial. Notably, treatment with the antioxidant N-acetyl cysteine (NAC) significantly reduced upregulation of the DNA damage marker γH2AX, subsequent ATM activation and cell death. In the Pmel mouse model of melanoma, the presence of NAC during ex vivo T cell expansion improved the persistence of adoptively transferred cells, reduced tumor growth and increased survival. Taken together, our results offer a preclinical proof of concept for the addition of NAC to current therapeutic T cell expansion protocols, offering immediate potential to improve the quality and therapeutic efficacy of adoptive T cell therapeutics infused into patients.

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“…A higher resistance of T cells to apoptosis in MS patients has been reported in several studies which found decreased expression of Fas and a lower rate of apoptosis induced by stimulation with mitogen in T cells from MS patients (49, 50). New data indicate that Th1 cells seem to be more susceptible for Fas-mediated apoptosis than Th17 cells, both in MS patients and healthy controls (51).…”

Section: Tolerancementioning

confidence: 60%

Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases

Riedhammer

Weissert

2015

Front. Immunol.

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Antigen presentation is in the center of the immune system, both in host defense against pathogens, but also when the system is unbalanced and autoimmune diseases like multiple sclerosis (MS) develop. It is not just by chance that a major histocompatibility complex gene is the major genetic susceptibility locus in MS; a feature that MS shares with other autoimmune diseases. The exact etiology of the disease, however, has not been fully understood yet. T cells are regarded as the major players in the disease, but most probably a complex interplay of altered central and peripheral tolerance mechanisms, T-cell and B-cell functions, characteristics of putative autoantigens, and a possible interference of environmental factors like microorganisms are at work. In this review, new data on all these different aspects of antigen presentation and their role in MS will be discussed, probable autoantigens will be summarized, and comparisons to other autoimmune diseases will be drawn.

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

Cited by 8 publications

References 18 publications

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

Efficacy of Adoptive T-cell Therapy Is Improved by Treatment with the Antioxidant N-Acetyl Cysteine, Which Limits Activation-Induced T-cell Death

Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases

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