Human immunoglobulin preparations for intravenous use prevent experimental autoimmune uveoretinitis

Abstract

We have evaluated the effect of human Igs for intravenous use (IVIg) on the onset and development of experimental autoimmune uveoretinitis (EAU), a T cell-dependent autoimmune disease induced in rats by a single immunization with retinal S-antigen (S-Ag). Five consecutive daily infusions of IVIg, starting on the same day as S-Ag immunization, protected (Lewis x Brown-Norway) F1 rats against EAU. The prevention of EAU was IVIg-specific, i.e. mediated by pooled human IgG from multiple donors, since neither infusions of BSA nor infusions of pooled Ig from only two healthy individuals were effective. Treatment with IVIg decreased lymphocyte proliferative and antibody responses to S-Ag and the proliferative response to concanavalin A. Lack of proliferation was not dependent upon generation of suppressor cells. Lymph node (LN) cells from IVIg-treated and S-Ag-immunized animals neither proliferated nor secreted IL-2 in response to S-Ag but proliferated when co-cultured with LN cells from rats immunized with S-Ag. Our findings are compatible with an induction of a state of functional inactivation/anergy of T lymphocytes by infusions of IVIg. This functional inactivation may be due to the presence in IVIg of antibodies that bind both in vivo and in vitro to rat lymphocytes. Results from the present study suggest a novel mechanism by which IVIg may be beneficial in human autoimmune diseases.