The role of IL-12 in the induction of intravenous tolerance in experimental autoimmune encephalomyelitis.
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.
Zhang
Guang-Xian
GX
Department of Neurology, University of Pennsylvania School of Medicine, Medical Center, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Xu
Hui
H
Kishi
Masahiko
M
Calida
Divina
D
Rostami
Abdolmohamad
A
D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D005260:Female; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D017634:Self Tolerance; D013116:Spinal Cord / Q000473:pathology
D001324:Autoantigens; D016207:Cytokines; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C405722:myelin basic protein 1-11; D018664:Interleukin-12