Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis.
BACKGROUND
Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist.


OBJECTIVE
To study the activation of CD4+ T cells, monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA.


METHODS
Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25(high) and CD26(high) cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS patients, the latter followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI) studies were conducted in all patients. Disease activity was assessed as relapses.


RESULTS
The median percentage of DCs expressing CD40 was 10% in untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05-1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers associated with regulatory, naïve or central memory T cell populations, but CD4+ T cell activation was not related with relapse risk.


CONCLUSIONS
MS patients treated with GA show prominent changes in circulating antigen-presenting cells and CD4+ T cells. Expression of CD40 on DCs is significantly lower and associated with relapse risk in MS patients treated with GA.
Danish Multiple Sclerosis Center, Copenhagen University Hospital Rigshospitalet, Denmark. sellebjerg@dadlnet.dk
F
F
Sellebjerg
D
D
Hesse
S
S
Limborg
H
H
Lund
H B
HB
Søndergaard
M
M
Krakauer
P S
PS
Sørensen
D000328:Adult; D000938:Antigen-Presenting Cells; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019013:CD40 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D000068717:Glatiramer Acetate; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008262:Macrophage Activation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D010455:Peptides / Q000627:therapeutic use*; D012008:Recurrence; D013601:T-Lymphocytes / Q000502:physiology*; D055815:Young Adult
D019013:CD40 Antigens; D059811:HLA-DRB1 Chains; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate