NORMAL IMMUNOGLOBULIN-G PROTECTS AGAINST EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY INDUCING TRANSFERABLE T-CELL UNRESPONSIVENESS TO MYELINBASIC-PROTEIN

Normal human IgG for intravenous use (IVIg), administered intraperiton eally, protected Lewis rats against experimental allergic encephalomye litis (EAE) induced by immunization with myelin basic protein (MBP). W e demonstrate that protection was associated with an acquired unrespon siveness of lymphocytes to MBP and a decreased ability of the cells to produce IL-2, IFN-gamma and TNF-alpha and, to a lesser degree, IL-4 a nd IL-10, in the presence of the antigen. Lymph node (LN) cells of pro tected rats failed to passively transfer EAE to naive syngeneic animal s. Our observations indicate that, rather than inducing selective immu ne deviation, IVIg induces preferential MBP unresponsiveness of Th1 ce lls. Whereas LN and splenic cells of IVIg-treated rats did not prolife rate nor secrete IL-2 in the presence of the antigen, proliferation wa s restored by adding exogeneous recombinant IL-2. In contrast, LN cell s of IVIg-treated rats proliferated normally and produced IL-2 in the presence of concanavalin A, indicating the selectivity for MBP of the anergy induced by IVlg when given at the time of immunization with the antigen. Treatment with IVlg also allowed a resistance to the seconda ry induction of EAE, indicating that IVlg protects from EAE but does n ot interfere with the processes that eventually lead to resistance to re-challenge. These data document the immunomodulatory effects of IVlg in T cell-dependent experimental autoimmune disease and further sugge st a role for normal Ig in the selection of functional T cell repertoi res.