Failure of glatiramer acetate to modify the peripheral T cell repertoire of relapsing–remitting multiple sclerosis patients

2010 ◽  
Vol 135 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Laureline Berthelot ◽  
Patrick Miqueu ◽  
Ségolène Pettré ◽  
Marina Guillet ◽  
Julien Moynard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Glatiramer Acetate ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

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 Lymphocyte subtypes in relapsing–remitting multiple sclerosis patients treated with dimethyl fumarate

2017 ◽  
Vol 3 (2) ◽  
pp. 205521731770293 ◽  
Author(s):  
C Chaves ◽  
R Ganguly ◽  
C Ceresia ◽  
A Camac
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
B Cell ◽  
Dimethyl Fumarate ◽  
Normal Lymphocyte ◽  
Cell Counts ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Recent data suggest that lymphopenia is more prevalent than reported in relapsing–remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF). Objective The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia. Method A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1, n = 35) and normal lymphocyte counts (G2, n = 24). Results Fifty-nine patients were identified, with mean age 49, 71.2% females, and average DMF duration 20 months. Age, sex, baseline white blood count, disease and treatment durations were similar between groups. Prior interferon therapy and baseline lower normal lymphocyte counts were more frequent in G1. Mean lymphocyte counts were 0.8 ± 0.2 × 109/L in G1 and 1.6 ± 0.3 × 109/L in G2. CD3+, CD4+, and CD8+ T cell mean counts were lower ( p < 0.0001), while CD4/CD8 ratio higher ( p = 0.03) in G1 than G2. Mean CD19 + B cell counts were normal; however, values were lower in G1 ( p = 0.04). After adjusting for confounders, significantly positive correlations were noted between lymphocyte counts and CD3 + , CD4+, CD8+ T, and B cell counts. Negative correlation was observed between lymphocyte counts and CD4/CD8 ratio driven by low CD8+ T cell counts. Conclusion DMF treatment predominantly impacts T cells, in particular CD8+ subtype. This finding may have implications in this population’s immunocompetence.

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