Induction of apoptosis of CD4+ T cells by immunomodulatory therapy of multiple sclerosis with glatiramer acetate.
Glatiramer acetate (GA), a mixture of synthetic polypeptides, has beneficial effects on the clinical course and the MRI-defined disease activity of patients with multiple sclerosis (MS). In MS, evidence has been provided that the apoptosis of disease-relevant T cells is dysregulated. In this study, we investigated the effect of GA on T cell apoptosis, T cell activation, and cytokine profile of lymphocytes derived from 19 relapsing-remitting MS patients during the first year of GA therapy. Analysis of blood samples obtained every 6 weeks showed an increase in apoptotic T helper cells after 30 weeks of therapy. This effect remained until the end of the study and was accompanied by an increase in activated T cells and interleukin-4-producing lymphocytes. Thus, in addition to the established effect of GA on the cytokine network, GA-mediated immunomodulation might involve the apoptotic elimination of T helper cells.
Rieks
Maike
M
Department of Neurology, Zentrum für klinische Forschung, Neuroimmunology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany. maike.rieks@ruhr-uni-bochum.de
Hoffmann
Volker
V
Aktas
Orhan
O
Juschka
Miriam
M
Spitzer
Iris
I
Brune
Nils
N
Schimrigk
Sebastian
S
Przuntek
Horst
H
Pöhlau
Dieter
D
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D013997:Time Factors; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000068717:Glatiramer Acetate; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D010455:Peptides; D000099192:CD69 Antigens