In vitro and in vivo inhibition of mitogen-driven T-cell activation by recombinant interferon beta.

Abstract

Recombinant interferon beta (rIFN beta) is being tested as experimental immunotherapy for exacerbating-remitting MS. To clarify the possible mechanisms of a therapeutic response to rIFN beta in MS patients, we conducted studies on the effects of rIFN beta on mitogen-driven T-cell activation by stimulating peripheral blood mononuclear cells (PBMC) with concanavalin A (ConA) or with anti-CD3 monoclonal antibodies in the presence or absence of rIFN beta. We monitored T-cell activation using proliferation assays or by expression of surface activation markers detected by flow cytometry. In vitro rIFN beta, in concentrations > or = 10 U/ml, inhibited PBMC proliferation or surface expression of interleukin-2 receptor (IL-2R), transferrin receptor, or CD2. In contrast, rIFN gamma augmented mitogen-driven IL-2R expression. PBMC isolated from normal volunteers or MS patients responded to ConA and rIFN beta in a similar manner. We conducted pilot in vivo studies in exacerbating-remitting MS patients participating in a double-blind placebo-controlled clinical trial of rIFN beta. PBMC were isolated from study participants immediately before and 24 hours after a weekly study injection. IL-2R expression by T cells was determined following a ConA stimulus. While there was no significant change following placebo injection, rIFN beta recipients showed significantly reduced ConA-driven IL-2R expression following study injection. The results document in vitro and in vivo inhibition of mitogen-driven T-cell activation by rIFN beta. This suggests a possible mechanism underlying a therapeutic response to rIFN beta in MS patients.