Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis.
Interferons (IFN) are biological molecules with anti-viral, anti-proliferative and immunomodulatory actions. There is evidence that IFN-gamma increases the frequency of exacerbations of multiple sclerosis (MS) whereas IFN-beta may reduce their frequency. Here we present evidence that IFN-beta significantly decreases concanavalin A (Con A)-induced proliferation of peripheral blood mononuclear cells (PBMC) of MS patients and healthy individuals. Similar results were obtained when PBMC were activated through the T cell receptor (TcR) by anti-CD3 monoclonal antibody or independently of it by phorbol ester and Ca2+ ionophore. These effects of IFN-beta were also noted when IFN-gamma and IFN-beta were added together. Furthermore, IFN-beta decreased proliferation when added to cells that were already pre-activated. Activated CD4+ and CD8+ T cells were downregulated to approximately the same extent. Analysis of cytokine production showed that IFN-gamma production by Con A activated PBMC was increased in MS when compared to controls. IFN-beta significantly decreased IFN-gamma production in MS patients and control individuals. Con A activated cultures treated with IFN-beta showed decreased IL2R expression and accumulation of IL2. These results show that IFN-beta decreases T cell activation and IFN-gamma production in vitro, effects that may be beneficial in MS.
Noronha
A
A
Department of Neurology, University of Chicago, IL 60637.
Toscas
A
A
Jensen
M A
MA
D000328:Adult; D000368:Aged; D015536:Down-Regulation; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma