Studies on the in vivo effects of interferon-beta (IFN beta) therapy on autoreactive T cells have never been carried out in multiple (MS). We investigated the T cell response to myelin basic protein (MBP), before and after IFN-beta therapy, raising MBP-specific T cell lines (TCL) from the peripheral blood of six MS patients with a satisfactory response to the treatment. IFN beta did not affect the relative frequency and epitope specificity of the TCL. After IFN beta therapy, the production of interleukin-4 was decreased in MBP-stimulated TCL while the secretion of interferon-gamma was increased in unstimulated TCL. Interleukin-10 and tumor necrosis factor-alpha did not show significant variations. This finding supports recent suggestions about the complexity of the T helper 1/T helper 2 paradigm in MS other organ-specific autoimmune diseases. In fact, the beneficial effects of IFN beta do not exclude an immunostimulatory action that involve potentially autoreactive T cells. This has implications for future treatment options, including combination therapies. (C) 1999 Elsevier Science B.V. All rights reserved.