INTERFERON-BETA INTERFERES WITH THE PROLIFERATION BUT NOT WITH THE CYTOKINE SECRETION OF MYELIN BASIC PROTEIN-SPECIFIC, T-HELPER TYPE-1 LYMPHOCYTES

Interferon-beta (IFN-beta) has beneficial effects on the frequency and severity of relapses, as well as on disease progression in patients s uffering from relapsing-remitting MS. Its mode of action, however, is not completely understood. Previous studies on T-lymphocyte bulk cultu res and T-lymphocyte lines with specificity for different antigens sug gested that the drug might partially act via suppression of T-cell pro liferation and secretion of proinflammatory cytokines like interferon- gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha). In t his study we investigated the effects of human recombinant IFN-beta(1b ) on proliferation, interleukin 2 (IL-2) receptor (IL-2R) alpha-chain upregulation, and cytokine and chemokine secretion of myelin basic pro tein-reactive, MS patient-derived T-cell clones secreting T-helper typ e 1 (Th1) cytokines. IFN-beta partially suppressed both antigen-and IL -2-driven proliferation of these cells without affecting the expressio n of either IL-2 or IL-2R alpha-chain. There was no inhibitory effect on the secretion of IFN-gamma, TNF-alpha, and macrophage inflammatory protein (MIP)-1 alpha, but release was rather slightly enhanced. In co nclusion, while IFN-beta does reduce proliferation of Th1-like, MBP-sp ecific T cells in vitro, the drug does not result in overall dysfuncti on of these cells. Therefore, the effect of IFN-beta on MS may not dep end on a primary inhibition of potentially encephalitogenic T lymphocy tes.