Glatiramer acetate (GA) induces IL-13/Il-5 secretion in naive T cells

In order to define possible mechanisms of immunomodulation by glatiramer ac etate (GA), we investigated the primary in vitro cytokine response of perip heral blood mononuclear cells (PBMCs) and T-cell subpopulations. In PBMCs f rom 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 concen trations. The response to GA was driven by the CD4(+)/CD45RA(+) T-cell subp opulation and was mediated by T-cell receptor (TCR) engagement as determine d by anti-TCR blocking antibodies, The findings are compatible with the hyp othesis that GA functions as partial or weak TCR-agonist activating naive T cells to produce the Th2 cytokines IL-13 and IL-5. (C) 2001 Elsevier Scien ce B.V. All rights reserved.