Interferon-beta-1a treatment increases CD56bright natural killer cells and CD4+CD25+ Foxp3 expression in subjects with multiple sclerosis

Vandenbark, Arthur A.; Huan, Jianya; Agotsch, Marisa; Tocha, Dorian La; Goelz, Susan; Offner, Halina; Lanker, Stefan; Bourdette, Dennis

doi:10.1016/j.jneuroim.2009.08.007

Cited by 90 publications

(62 citation statements)

References 21 publications

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“…2 CD56 bright NK cells may be involved in the control of the immune responses, mainly through the production of anti-inflammatory molecules (7)(8)(9)(10)(11). Moreover, a correlation between the clinical success of antiinflammatory treatments and the expansion of CD16 2 CD56…”

Section: Discussionmentioning

confidence: 99%

“…2 CD56 bright NK cells (10). Similarly, treatment of multiple sclerosis patients with daclizumab, a humanized anti-IL-2Ra Ab, led to the expansion of PB CD16 2 CD56 bright NK cells, which was correlated with decreased T cell survival and better prognosis (11 Regulation of the immune responses may be achieved through the expression and/or release of different molecules by immunoregulatory cells.…”

Section: Cd56mentioning

confidence: 99%

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CD56brightCD16− NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation

Morandi

Horenstein

Chillemi

et al. 2015

The Journal of Immunology

119

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Recent studies suggested that human CD56brightCD16− NK cells may play a role in the regulation of the immune response. Since the mechanism(s) involved have not yet been elucidated, in the present study we have investigated the role of nucleotide-metabolizing enzymes that regulate the extracellular balance of nucleotides/nucleosides and produce the immunosuppressive molecule adenosine (ADO). Peripheral blood CD56dimCD16+ and CD56brightCD16− NK cells expressed similar levels of CD38. CD39, CD73, and CD157 expression was higher in CD56brightCD16− than in CD56dimCD16+ NK cells. CD57 was mostly expressed by CD56dimCD16+ NK cells. CD203a/PC-1 expression was restricted to CD56brightCD16− NK cells. CD56brightCD16− NK cells produce ADO and inhibit autologous CD4+ T cell proliferation. Such inhibition was 1) reverted pretreating CD56brightCD16− NK cells with a CD38 inhibitor and 2) increased pretreating CD56brightCD16− NK cells with a nucleoside transporter inhibitor, which increase extracellular ADO concentration. CD56brightCD16− NK cells isolated from the synovial fluid of juvenile idiopathic arthritis patients failed to inhibit autologous CD4+ T cell proliferation. Such functional impairment could be related to 1) the observed reduced CD38/CD73 expression, 2) a peculiar ADO production kinetics, and 3) a different expression of ADO receptors. In contrast, CD56brightCD16− NK cells isolated from inflammatory pleural effusions display a potent regulatory activity. In conclusion, CD56brightCD16− NK cells act as “regulatory cells” through ADO produced by an ectoenzymes network, with a pivotal role of CD38. This function may be relevant for the modulation of the immune response in physiological and pathological conditions, and it could be impaired during autoimmune/inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Cd56mentioning

confidence: 99%

CD56brightCD16− NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation

Morandi

Horenstein

Chillemi

et al. 2015

The Journal of Immunology

119

View full text Add to dashboard Cite

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“…decrease of the cytotoxic CD56dim NK cells in the periphery [53][54][55][56]. Of interest, the change in NK differentiation state and NK receptor expression in response to IFNβ has also been associated with clinical response [57].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

McKay

Gatt

Fewings

et al. 2016

Clinical Immunology

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Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p < 0.028 for TBX21) and demonstrate longitudinal stability (p<10 -4 ) and high heritability (h 2 =0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were underrepresented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.

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“…The persistence of neutralizing antibodies to IFN-β predicts clinically active disease (39), while an inhibited expression of CD49d antigens on T-cells may serve as a marker of treatment efficacy during the administration of with natalizumab, a monoclonal antibody to that molecule (40). Furthermore, the frequency of CD4 + CD25 + Treg cells expressing Foxp3 has recently been successfully used to assess the effects of IFN-β therapy (41,42).…”

Section: Monitoring and Assessment Of Treatment Effectsmentioning

confidence: 99%

Biomarkers for Multiple Sclerosis

Tomioka

Matsui

2014

Intern. Med.

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Magnetic resonance imaging has been shown to be a powerful tool for diagnosing multiple sclerosis (MS) and evaluating surrogate markers of the disease activity. However, biomarkers may provide more accurate information regarding ongoing immune responses leading to demyelination and treatment effects in MS patients. Although serum biomarkers are easily accessible, they do not provide clear-cut results, whereas cerebrospinal fluid (CSF) biomarkers provide unequivocal information, although samples cannot be repeatedly obtained. For diagnosis, the presence of oligoclonal IgG bands remains important. In addition, measuring the levels of adhesion molecules, matrix metalloproteinase-9 and complement regulator factor H in the serum and evaluating the proportion of Th1/Th2 cells in the blood may be clinically feasible for monitoring the disease activity. In CSF samples, increased IL-8, IL-12, IL-17, CCL3, CCL5 and CXCL10 levels indicate active disease, and the flow cytometry findings of CSF cells can be used to detect increases in Th1 and CD4 + CD25 + cells during relapse. Biomarkers closely linked to the disease activity may be informative of the pathogenesis of MS, while those associated with tissue damage or repair may be targets of new treatment strategies. Establishing the latter will be a primary point of research in the near future.

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Interferon-beta-1a treatment increases CD56bright natural killer cells and CD4+CD25+ Foxp3 expression in subjects with multiple sclerosis

Cited by 90 publications

References 21 publications

CD56brightCD16− NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation

CD56brightCD16− NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

Biomarkers for Multiple Sclerosis

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