J Immunol 2002 Mar 1;168(5):2501-7
Zhang GX, Xu H, Kishi M, Calida D, Rostami A.
Department of Neurology, University of Pennsylvania School of Medicine, Medical Center, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Intravenous administration of autoantigen is an effective method to induce Ag-specific tolerance against experimental autoimmune encephalomyelitis (EAE).
IL-12 is a potent Th1 stimulator and an essential cytokine in the induction of EAE.
The role of IL-12 in the induction of i.v. tolerance is not clear.
In this study, we induced tolerance by i.v. administering myelin basic protein (MBP) peptide Ac1-11 (MBP1-11) in EAE.
We observed significant suppression of IL-12 production by the lymph node cells of MBP1-11-injected mice.
To see whether the low level of IL-12 is the cause or effect of tolerance, we administered IL-12 to the EAE mice at the time of i.v. MBP1-11 injection.
Exogenous IL-12 abrogated the suppression of clinical and pathological EAE by i.v. tolerance.
IL-12 blocked the suppressive effect of i.v. tolerance on the proliferative response to MBP1-11 and MBP1-11-induced production of IL-12 and IFN-gamma.
Furthermore, IL-12 completely blocked the i.v. tolerance-induced type 1 T regulatory cell response.
These data suggest that i.v. administration of autoantigen results in the suppression of endogenous IL-12 and the consequent switching of the immune response from an immunogenic to a tolerogenic form.