Minor myelin proteins can be majot targets for peripheral blood T cells from both multiple sclerosis patients and healthy subjects

Objective: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). Background: MS is an immune-mediated disease and cytokines have been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. Methods: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T cells were analyzed for IFN-g, IL-2, TNF-a, IL-4, IL-10 and IL-13 production. Results: MS patients express significantly more CD4+ and CD8+ T cells producing IFN-g compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-a and a significant increase in CD8+ T cells producing IL-4 and IL-10. Conclusions: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.

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Potassium channel expression in human CD4+ regulatory and naïve T cells from healthy subjects and multiple sclerosis patients

Immunology Letters ◽

10.1016/j.imlet.2009.04.008 ◽

2009 ◽

Vol 124 (2) ◽

pp. 95-101 ◽

Cited By ~ 15

Author(s):

Zoltan Varga ◽

Tunde Csepany ◽

Ferenc Papp ◽

Akos Fabian ◽

Peter Gogolak ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Potassium Channel ◽

Healthy Subjects ◽

Naive T Cells ◽

Naïve T Cells ◽

Channel Expression ◽

Multiple Sclerosis Patients

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Adenosine Deaminase and 5′Nucleotidase Activities in Peripheral Blood T Cells of Multiple Sclerosis Patients

Neurochemical Research ◽

10.1007/s11064-005-2680-6 ◽

2005 ◽

Vol 30 (4) ◽

pp. 453-456 ◽

Cited By ~ 9

Author(s):

S. Vivekanandhan ◽

C. C. Soundararajan ◽

M. Tripathi ◽

M. C. Maheshwari

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Adenosine Deaminase ◽

Peripheral Blood ◽

Multiple Sclerosis Patients

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Clonal expansion and decreased occurrence of peripheral blood gamma delta T cells of the V delta 2J delta 3 lineage in multiple sclerosis patients

International Immunology ◽

10.1093/intimm/9.7.1031 ◽

1997 ◽

Vol 9 (7) ◽

pp. 1031-1041 ◽

Cited By ~ 4

Author(s):

W Liedtke

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Peripheral Blood ◽

Clonal Expansion ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Multiple Sclerosis Patients

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Interferon gamma and interleukin 4 producing T cells in peripheral blood of multiple sclerosis patients undergoing immunomodulatory treatment

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.74.1.123 ◽

2003 ◽

Vol 74 (1) ◽

pp. 123-126 ◽

Cited By ~ 26

Author(s):

D Franciotta

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Interferon Gamma ◽

Peripheral Blood ◽

Interleukin 4 ◽

Immunomodulatory Treatment ◽

Multiple Sclerosis Patients

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Increase of CD4+TNFα+IL-2−T cells in cerebrospinal fluid of multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458508096871 ◽

2009 ◽

Vol 15 (1) ◽

pp. 120-123 ◽

Cited By ~ 9

Author(s):

N Shi ◽

Y Kawano ◽

T Matsuoka ◽

FJ Mei ◽

T Ishizu ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cerebrospinal Fluid ◽

Peripheral Blood ◽

Neurological Diseases ◽

Significant Change ◽

Multiple Sclerosis Patients

Intracellular production of TNFα and IL-2 after stimulation with phorbol myristate/ionomycin was flowcytometrically measured in CD4+ T cells from peripheral blood (PB) and cerebrospinal fluid (CSF) of 29 patients with multiple sclerosis (MS), and 16 with other inflammatory and 41 with other non-inflammatory neurological diseases. In CSF, the percentages of CD4+TNFα+IL-2−T cells were significantly higher in patients with MS than either of the controls, whereas no difference was found in CD4+TNFα+IL-2+T or CD4+TNFα−IL-2+T cells. The increase was more pronounced at relapse than in remission. No significant change was detected in PB. These findings suggested that CD4+TNFα+IL-2−T cells are intrathecally upregulated in MS.

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Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains

Frontiers in Neurology ◽

10.3389/fneur.2021.801097 ◽

2022 ◽

Vol 12 ◽

Author(s):

Sophie A. H. Jacobs ◽

Paolo A. Muraro ◽

Maria T. Cencioni ◽

Sarah Knowles ◽

James H. Cole ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

T Cell ◽

Cellular Senescence ◽

Peripheral Blood ◽

Physical Disability ◽

Brain Health ◽

Cell Frequency ◽

Multiple Sclerosis Patients ◽

Brain Age

Background: Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has been reported in MS using T-cell biomarker CD8+CD57+.Objective: Here we explored links between MRI-derived brain-age and blood-derived cellular senescence. We examined the value of combining brain-PAD with CD8+CD57+(ILT2+PD-1+) T-cells when predicting disability score in MS and considered whether age-related biological mechanisms drive disability.Methods: Brain-age analysis was applied to T1-weighted MRI images. Disability was assessed and peripheral blood was examined for CD8+CD57+ T-cell phenotypes. Linear regression models were used, adjusted for sex, age and normalized brain volume.Results: We included 179 mainly relapsing-remitting MS patients. A high brain-PAD was associated with high physical disability (mean brain-PAD = +6.54 [5.12–7.95]). CD8+CD57+(ILT2+PD-1+) T-cell frequency was neither associated with disability nor with brain-PAD. Physical disability was predicted by the interaction between brain-PAD and CD8+CD57+ILT2+PD-1+ T-cell frequency (AR2 = 0.196), yet without improvement compared to brain-PAD alone (AR2 = 0.206; AICc = 1.8).Conclusion: Higher frequency of CD8+CD57+ILT2+PD-1+ T-cells in the peripheral blood in patients with an older appearing brain was associated with worse disability scores, suggesting a role of these cells in the development of disability in MS patients with poorer brain health.

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