Glatiramer acetate (GA) induces IL-13/IL-5 secretion in naive T cells.
In order to define possible mechanisms of immunomodulation by glatiramer acetate (GA), we investigated the primary in vitro cytokine response of peripheral blood mononuclear cells (PBMCs) and T-cell subpopulations. In PBMCs from healthy subjects and untreated patients with multiple sclerosis (MS) GA-induced T-cell proliferation and mRNA expression/cytokine, secretion of IL-13 and IL-5 but not of IL-10, TGF-beta or IL-12, IL-4 was detected at the mRNA level only. IFN-gamma was induced in a few subjects at very low concentrations. The response to GA was driven by the CD4(+)/CD45RA(+) T-cell subpopulation and was mediated by T-cell receptor (TCR) engagement as determined by anti-TCR blocking antibodies. The findings are compatible with the hypothesis that GA functions as partial or weak TCR-agonist activating naive T cells to produce the Th2 cytokines IL-13 and IL-5.
Wiesemann
E
E
Department of Neurology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30623, Hannover, Germany.
Klatt
J
J
Sönmez
D
D
Blasczyk
R
R
Heidenreich
F
F
Windhagen
A
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D018793:Interleukin-13 / Q000097:blood*; D015848:Interleukin-5 / Q000097:blood*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood*; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D015848:Interleukin-5; D010455:Peptides; D000068717:Glatiramer Acetate