T cells from multiple sclerosis patients recognize immunoglobulin G from cerebrospinal fluid

2003 ◽  
Vol 9 (3) ◽  
pp. 228-234 ◽  
Author(s):  
T Holmøy ◽  
B Vandvik ◽  
F Vartdal
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
T Cell ◽  
Mononuclear Cells ◽  
Neurological Diseases ◽  
Affinity Maturation ◽  
Peripheral Blood Mononuclear ◽  
Number Of Patients ◽  
Multiple Sclerosis Patients

Idiotopic sequences are created after V, D and J recombinations and by somatic mutations during affinity maturation of immuglobulin (Ig) molecules, and may therefore be potential immunogenic epitopes. Idiotope-specific T cells are able to activate and sustain the B cells producing such idiotopes. It is therefore possible that idiotope-specific intrathecal T cells could help maintain the persisting intrathecal synthesis of oligoclonal IgG observed in patients with multiple sclerosis (MS). This study was undertaken to examine T-cell responses to cerebrospinal fluid (CSF) IgG. Peripheral blood mononuclear cells (PBMC) from 14 of 21 MS patients and four of 17 control patients with other neurological diseases proliferated upon stimulation with autologous C SF IgG, while five and three, respectively, responded to serum IgG. By comparison, responses to myelin basic protein were recorded in only four MS and three control patients. Data from a limited number of patients indicate that the C SF IgG responsive cells were CD4+ and human leucocyte antigen DR restricted, that PBMC also respond to C SF IgG from other MS patients and that the C SF may contain T cells responding to autologous C SF IgG. This suggests that C SF IgG, or substances bound to this IgG, may represent T-cell immunogens, which could contribute to the intrathecal immune response in MS.

scholarly journals The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 101
Author(s):  
Ivet A. Yordanova ◽  
Friederike Ebner ◽  
Axel Ronald Schulz ◽  
Svenja Steinfelder ◽  
Berit Rosche ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Clinical Efficacy ◽  
Mononuclear Cells ◽  
Phase 1 ◽  
Th2 Cells ◽  
Continuous Increase ◽  
Trichuris Suis ◽  
Multiple Sclerosis Patients

Considering their potent immunomodulatory properties, therapeutic applications of Trichuris suis ova (TSO) are studied as potential alternative treatment of autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), or inflammatory bowel disease (IBD). Clinical phase 1 and 2 studies have demonstrated TSO treatment to be safe and well tolerated in MS patients, however, they reported only modest clinical efficacy. We therefore addressed the cellular and humoral immune responses directed against parasite antigens in individual MS patients receiving controlled TSO treatment (2500 TSO p.o. every 2 weeks for 12 month). Peripheral blood mononuclear cells (PBMC) of MS patients treated with TSO (n = 5) or placebo (n = 6) were analyzed. A continuous increase of serum IgG and IgE antibodies specific for T. suis excretory/secretory antigens was observed up to 12 months post-treatment. This was consistent with mass cytometry analysis identifying an increase of activated HLA-DRhigh plasmablast frequencies in TSO-treated patients. While stable and comparable frequencies of total CD4+ and CD8+ T cells were detected in placebo and TSO-treated patients over time, we observed an increase of activated HLA-DR+CD4+ T cells in TSO-treated patients only. Frequencies of Gata3+ Th2 cells and Th1/Th2 ratios remained stable during TSO treatment, while Foxp3+ Treg frequencies varied greatly between individuals. Using a T. suis antigen-specific T cell expansion assay, we also detected patient-to-patient variation of antigen-specific T cell recall responses and cytokine production. In summary, MS patients receiving TSO treatment established a T. suis-specific T- and B-cell response, however, with varying degrees of T cell responses and cellular functionality across individuals, which might account for the overall miscellaneous clinical efficacy in the studied patients.

Immunoglobulin-like transcript 3, an inhibitor of T cell activation, is reduced on blood monocytes during multiple sclerosis relapses and is induced by interferon β-1b

2009 ◽  
Vol 16 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Mark A Jensen ◽  
Rachel N Yanowitch ◽  
Anthony T Reder ◽  
David M White ◽  
Barry GW Arnason
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Mononuclear Cells ◽  
Interferon Β ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Immunoglobulin-like transcripts (ILTs) are immunoregulatory proteins that either activate or inhibit immune responses. ILT3 is inhibitory and is expressed preferentially by antigen-presenting cells. When its extracellular domain binds to an unidentified ligand of activated T cells, the T cell is silenced. Our objective was to study the expression of ILT3 on circulating monocytes in RRMS. Freshly isolated peripheral blood mononuclear cells were analyzed by multicolored flow cytometry. The proportion of ILT3+CD14+ monocytes in blood, and ILT3 levels expressed by them, is lower in untreated multiple sclerosis in relapse than in: (1) untreated multiple sclerosis in remission (p < 0.009); (2) stable interferon β-treated relapsing—remitting multiple sclerosis (p < 0.001) and; (3) healthy controls (p < 0.009). Glatiramer acetate-stimulated CD4 + T cells, co-cultured with freshly isolated monocytes, proliferate significantly better (p = 0.0017 for multiple sclerosis; p = 0.0015 for controls) when T cell interaction with monocyte-expressed ILT3 is blocked by anti-ILT3 antibody. Interferon β is beneficial in multiple sclerosis; why so remains unclear. Interferon β-1b markedly increases ILT3 expression in vitro by monocytes from multiple sclerosis patients and controls. These findings identify a putative novel mechanism for the therapeutic benefit bestowed by Interferon β and a new target for therapeutic intervention in relapsing—remitting multiple sclerosis.

scholarly journals Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

2017 ◽  
Vol 114 (40) ◽  
pp. 10713-10718 ◽  
Author(s):  
Egle Cekanaviciute ◽  
Bryan B. Yoo ◽  
Tessel F. Runia ◽  
Justine W. Debelius ◽  
Sneha Singh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Gut Bacteria ◽  
The Body ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Cell Functions ◽  
Multiple Sclerosis Patients

The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10–expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice “humanized” with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.

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

2009 ◽  
Vol 15 (1) ◽  
pp. 120-123 ◽  
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.

scholarly journals Interferon-beta changes the expression of IL10, IL23A and FOXP3 on Multiple Sclerosis patients' T cells

2021 ◽  
Author(s):  
Hazal Gezmis ◽  
Tansu Doran ◽  
Saime Fusun Mayda Domac ◽  
Deniz Yucel ◽  
Rahsan Karaci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Disease Progression ◽  
Drug Concentration ◽  
Interferon Beta ◽  
Mononuclear Cells ◽  
Therapeutic Effects ◽  
Gene Expressions ◽  
Peripheral Blood Mononuclear ◽  
Multiple Sclerosis Patients

Aim of the Study: Multiple sclerosis (MS) is an autoimmune disorder causing demyelination in axons. Available therapies target different molecules, but not all have therapeutic effects on disease progression, and this effect can only be seen after a long-time administration. Interferon beta (IFN-β), an MS therapy for many years, slows down the disease progression and reduces disease symptoms by targeting T cells. Yet, a considerable portion of the patient has experienced no therapeutic response to IFN-β. It is necessary to determine disease-specific biomarkers which allow early diagnosis or treatment of MS. Here, it was aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A) as well as forkhead box P3 (FOXP3) genes on MS after IFN-β therapy. Materials & Methods: Peripheral blood mononuclear cells (PBMCs) were extracted to isolate CD4+ and CD25+ T cells. Cytotoxicity assays were performed on each cell type for determining optimum drug concentration. Then, cells were cultured and determined drug concentration was administered to the cells to measure gene expressions with RT-PCR. Results: It was found that the cytotoxic effect of IFN-β was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFN-β. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48h in CD4+ T cells. For CD25+ T cells, the graded increase of FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake, significantly. Conclusion: Although considerable change in expression was obtained, the long-term IFN-β effect on both genes and cells should be determined by follow-up at least a year. Keywords: MS, IFN-β, IL23A, FOXP3, IL10, T cells

scholarly journals Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 12 ◽  
Author(s):  
Stefan Gingele ◽  
Thais Jacobus ◽  
Franz Konen ◽  
Martin Hümmert ◽  
Kurt-Wolfram Sühs ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
B Cells ◽  
Mononuclear Cells ◽  
Significant Proportion ◽  
Multicolor Flow Cytometry ◽  
Peripheral Blood Mononuclear ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Multiple Sclerosis Patients

Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS). CD20 is mainly expressed by B cells, but a subset of T cells (CD3+CD20+ T cells) also expresses CD20, and these CD20+ T cells are known to be a highly activated cell population. The blood of MS patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3+ T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45+ lymphocytes, and constituted a significant proportion (18.4%) of all CD20+ cells. CD3+CD20+ T cells and CD19+CD20+ B cells were effectively depleted two weeks after a single administration of 300 mg ocrelizumab. Our results demonstrate that treatment with ocrelizumab does not exclusively target B cells, but also CD20+ T cells, which account for a substantial amount of CD20-expressing cells. Thus, we speculate that the efficacy of ocrelizumab might also be mediated by the depletion of CD20-expressing T cells.

Class I–unrestricted noncytotoxic anti–HTLV-I activity of CD8+ T cells

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1994-1995 ◽  
Author(s):  
Masako Moriuchi ◽  
Hiroyuki Moriuchi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Membrane Filter ◽  
Cd8 T Cell ◽  
Class I ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Permeable Membrane

Abstract Although it is widely believed that viral clearance is mediated principally by the destruction of infected cells by cytotoxic T cells, noncytolytic antiviral activity of CD8+ T cells may play a role in preventing the progression to disease in infections with immunodeficiency viruses and hepatitis B virus. We demonstrate here that (1) replication of human T-lymphotropic virus type I (HTLV-I) is more readily detected from CD8+ T-cell–depleted (CD8−) peripheral blood mononuclear cells (PBMCs) of healthy HTLV-I carriers than from unfractionated PBMCs, (2) cocultures of CD8− PBMCs with autologous or allogeneic CD8+ T cells suppressed HTLV-I replication, and (3) CD8+ T-cell anti-HTLV-I activity is not abrogated intrans-well cultures in which CD8+ cells are separated from CD8− PBMCs by a permeable membrane filter. These results suggest that class I-unrestricted noncytolytic anti–HTLV-I activity is mediated, at least in part by a soluble factor(s), and may play a role in the pathogenesis of HTLV-I infection.

scholarly journals Multiple sclerosis patients have reduced resting and increased activated CD4+CD25+FOXP3+T regulatory cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nirupama D. Verma ◽  
Andrew D. Lam ◽  
Christopher Chiu ◽  
Giang T. Tran ◽  
Bruce M. Hall ◽  
...  
Keyword(s):  
T Cells ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Effector Memory ◽  
Regulatory Cells ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Treg Population ◽  
Multiple Sclerosis Patients ◽  
Population Iii

AbstractResting and activated subpopulations of CD4+CD25+CD127loT regulatory cells (Treg) and CD4+CD25+CD127+ effector T cells in MS patients and in healthy individuals were compared. Peripheral blood mononuclear cells isolated using Ficoll Hypaque were stained with monoclonal antibodies and analysed by flow cytometer. CD45RA and Foxp3 expression within CD4+ cells and in CD4+CD25+CD127loT cells identified Population I; CD45RA+Foxp3+, Population II; CD45RA−Foxp3hi and Population III; CD45RA−Foxp3+ cells. Effector CD4+CD127+ T cells were subdivided into Population IV; memory /effector CD45RA− CD25−Foxp3− and Population V; effector naïve CD45RA+CD25−Foxp3−CCR7+ and terminally differentiated RA+ (TEMRA) effector memory cells. Chemokine receptor staining identified CXCR3+Th1-like Treg, CCR6+Th17-like Treg and CCR7+ resting Treg. Resting Treg (Population I) were reduced in MS patients, both in untreated and treated MS compared to healthy donors. Activated/memory Treg (Population II) were significantly increased in MS patients compared to healthy donors. Activated effector CD4+ (Population IV) were increased and the naïve/ TEMRA CD4+ (Population V) were decreased in MS compared to HD. Expression of CCR7 was mainly in Population I, whereas expression of CCR6 and CXCR3 was greatest in Populations II and intermediate in Population III. In MS, CCR6+Treg were lower in Population III. This study found MS is associated with significant shifts in CD4+T cells subpopulations. MS patients had lower resting CD4+CD25+CD45RA+CCR7+ Treg than healthy donors while activated CD4+CD25hiCD45RA−Foxp3hiTreg were increased in MS patients even before treatment. Some MS patients had reduced CCR6+Th17-like Treg, which may contribute to the activity of MS.

scholarly journals Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

2021 ◽  
Author(s):  
L. Sams ◽  
S. Kruger ◽  
V. Heinemann ◽  
D. Bararia ◽  
S. Haebe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Prognostic Information ◽  
Peripheral Blood Mononuclear

Abstract Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

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