Human immunoglobulin preparations for intravenous use prevent experimental autoimmune uveoretinitis

We have evaluated the effect of human Igs for intravenous use(IVIg) on the onset and development of experimental autoimmuneuveoretinitis (EAU), a T cell-dependent autoimmune disease inducedin rats by a single immunization with retinal S-antigen (S-Ag).Five consecutive daily infusions of IVIg, starting on the sameday as S-Ag immunization, protected (Lewis x Brown-Norway) F¹rats against EAU. The prevention of EAU was IVIg-specific, i.e.mediated by pooled human IgG from multiple donors, since neitherinfusions of BSA nor infusions of pooled Ig from only two healthyindividuals were effective. Treatment with IVIg decreased lymphocyteprollferative and antibody responses to S-Ag and the proliferativeresponse to concanavalin A. Lack of proliferation was not dependentupon generation of suppressor cells. Lymph node (LN) cells fromIVIg-treated and S-Ag-immunized animals neither proliferatednor secreted IL-2 in response to S-Ag but proliferated whenco-cultured with LN cells from rats immunized with S-Ag. Ourfindings are compatible with an induction of a state of functionalinactivatlon/anergy of T lymphocytes by infusions of IVIg. Thisfunctional inactivation may be due to the presence in IVIg ofantibodies that bind both in vivo and in vitro to rat lymphocytes.Results from the present study suggest a novel mechanism bywhich IVIg may be beneficial in human autoimmune diseases.