Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease that serves as an animal model for multiple sclerosis. Oral administration of myelin basic protein (MBP) suppresses EAE by inducing peripheral tolerance. T cell clones were isolated from the mesenteric lymph nodes of SJL mice that had been orally tolerized to MBP. These clones were CD4+ and were structurally identical to T helper cell type 1 (TH1) encephalitogenic CD4+ clones in T cell receptor usage, major histocompatibility complex restriction, and epitope recognition. However, they produced transforming growth factor-beta with various amounts of interleukin-4 and interleukin-10 and suppressed EAE induced with either MBP or proteolipid protein. Thus, mucosally derived TH2-like clones induced by oral antigen can actively regulate immune responses in vivo and may represent a different subset of T cells.
Chen
Y
Y
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Kuchroo
V K
VK
Inobe
J
J
Hafler
D A
DA
Weiner
H L
HL
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008285:Major Histocompatibility Complex; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology; D018991:Myelin Proteolipid Protein; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000939:Epitopes; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4