INTRAVENOUS IMMUNOGLOBULIN TREATMENT OF EXPERIMENTAL T-CELL-MEDIATED AUTOIMMUNE-DISEASE - UP-REGULATION OF T-CELL PROLIFERATION AND DOWN-REGULATION OF TUMOR-NECROSIS-FACTOR-ALPHA SECRETION

It has been reported previously that intravenous administration of nor mal human immunoglobulins (IVIg) to human patients can suppress the cl inical signs of certain autoimmune diseases. However, the mechanism(s) by which normal Ig interferes with the various disorders and the sche duling of treatment have been poorly delineated. To study these questi ons, we examined IVIg treatment of two experimentally induced T cell a utoimmune diseases in rats: experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA). We now report that IVIg treatment ( 0.4 g/kg) inhibited the active induction of both EAE and AA, and that this treatment did not affect the acquisition of resistance to reinduc tion of EAE. The importance of the site of administration and schedule of treatment were studied in the AA model. Ig was effective when give n intravenously, but not when administrated subcutaneously or intraper itoneally. IVIg treatment was effective,when given daily from immuniza tion to outbreak of disease; but it was also effective when given once at the time of immunization or once 2 wk after induction of AA, just at the clinical outbreak of disease. Administration of IVIg between im munization and outbreak of AA was less effective. Prevention of diseas e by IVIg occurred despite the presence of T cell reactivity to the sp ecific antigens in the disease. In fact, IVIg administrated to naive r ats activated T cell reactivity to some self-antigens. Nevertheless, I VIg treatment led to decreased production of the inflammatory cytokine TNF alpha. Thus, IVIg treatment may exert its therapeutic power not b y inhibiting T cell recognition of self-antigens, but by inhibiting th e biological consequences of T cell recognition.