Epicutaneously induced TGF-beta-dependent tolerance inhibits experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) with limited treatment modalities. To evaluate the efficacy of epicutaneous (e.c.) tolerance induction in the prevention of CNS autoimmunity, we utilized an animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE). We show that application of myelin basic protein (MBP) to the skin prior to the induction of EAE by immunization with MBP protected mice from developing disease. In addition, e.c. application of MBP at the first clinical signs of EAE, also resulted in suppression of disease. This therapeutic effect was transferable to naïve recipients with lymph node cells from MBP-treated mice. These regulatory cells were found to be antigen non-specific, as suppression of EAE also occurred when the foreign antigens OVA or TNP were e.c. applied. The mechanistic basis for the tolerance was found to be the production of TGF-beta by the antigen induced toleragenic regulatory T cells. These data demonstrate that e.c.-induced regulatory T cells are potent inhibitors of antigen-specific T cell responses, and suggest that e.c. tolerization may have potential effectiveness in the treatment of autoimmune disorders.
Szczepanik
Marian
M
Department of Human Developmental Biology, Jagiellonian University, College of Medicine, ul. Kopernika 7, 31-034 Kraków, Poland.
Tutaj
Monika
M
Bryniarski
Krzysztof
K
Dittel
Bonnie N
BN
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007108:Immune Tolerance / Q000502:physiology; D007116:Immunization, Passive / Q000379:methods; D007279:Injections, Subcutaneous / Q000379:methods; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D004676:Myelin Basic Protein / Q000008:administration & dosage* / Q000276:immunology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016207:Cytokines; D004676:Myelin Basic Protein; D016212:Transforming Growth Factor beta