Rituximab reduces B cells and T cells in cerebrospinal fluid of 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.

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Cerebrospinal fluid B cells from multiple sclerosis patients are subject to normal germinal center selection

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2006.10.020 ◽

2007 ◽

Vol 183 (1-2) ◽

pp. 189-199 ◽

Cited By ~ 45

Author(s):

Christopher Harp ◽

Jane Lee ◽

Doris Lambracht-Washington ◽

Elizabeth Cameron ◽

Gregory Olsen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

B Cells ◽

Germinal Center ◽

Multiple Sclerosis Patients

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Relative increase of inflammatory CD4+ T cells in the cerebrospinal fluid of multiple sclerosis patients and control individuals

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1990.tb05120.x ◽

2008 ◽

Vol 79 (1) ◽

pp. 15-20 ◽

Cited By ~ 7

Author(s):

F. T. M. ROTTEVEEL ◽

B. KUENEN ◽

I. KOKKELINK ◽

A. MEAGER ◽

C. J. LUCAS

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cerebrospinal Fluid ◽

Cd4 T Cells ◽

Relative Increase ◽

Multiple Sclerosis Patients ◽

And Control

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HLA-E restricted CD8+ T cell subsets are phenotypically altered in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458513509703 ◽

2013 ◽

Vol 20 (7) ◽

pp. 790-801 ◽

Cited By ~ 8

Author(s):

Kim Pannemans ◽

Bieke Broux ◽

An Goris ◽

Bénédicte Dubois ◽

Tom Broekmans ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

T Cell ◽

B Cells ◽

T Cell Subsets ◽

Regulatory Role ◽

T And B Cells ◽

Autoreactive T Cell ◽

Multiple Sclerosis Patients

Background: The importance of Qa-1 restricted CD8+ T cells in regulating autoreactive T cell responses has been demonstrated in animal models for autoimmune disorders, including multiple sclerosis (MS). Objective: We hypothesize that their human variant, HLA-E restricted CD8+ T cells, fulfills a similar regulatory role in man and that these cells are of importance in MS. Methods: A large cohort of MS patients and healthy controls was genotyped for the two known HLA-E polymorphisms. Flow cytometry was used to determine HLA-E expression kinetics and to phenotype HLA-E restricted CD8+ T cells. Immunohistochemistry was performed to investigate HLA-E expression in the central nervous system (CNS) of MS patients. Results: HLA-E is upregulated on immune cells upon in vitro activation and this upregulation is polymorphism-dependent for T and B cells. T and B cells in lesions of MS patients show enhanced HLA-E expression. Furthermore, NKG2C+CD8+ T cells of MS patients have a significantly lower Foxp3 expression, while NKG2A+CD8+ T cells of MS patients produce higher levels of pro-inflammatory cytokines compared to those of healthy individuals. Conclusion: Our study indicates that the HLA-E system is altered in MS and could play a regulatory role in disease.

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Intracerebral Human Regulatory T Cells: Analysis of CD4+CD25+FOXP3+ T Cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients

PLoS ONE ◽

10.1371/journal.pone.0017988 ◽

2011 ◽

Vol 6 (3) ◽

pp. e17988 ◽

Cited By ~ 54

Author(s):

Benedikt Fritzsching ◽

Jürgen Haas ◽

Fatima König ◽

Pierre Kunz ◽

Eva Fritzsching ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cerebrospinal Fluid ◽

Regulatory T Cells ◽

Brain Lesions ◽

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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Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients

Cells ◽

10.3390/cells8010012 ◽

2018 ◽

Vol 8 (1) ◽

pp. 12 ◽

Cited By ~ 23

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.

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