Costimulation-dependent modulation of experimental autoimmune encephalomyelitis by ligand stimulation of V alpha 14 NK T cells.
Experimental autoimmune encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease that can be protected against by stimulating regulatory cells. Here we examined whether EAE can be purposefully modulated by stimulating Valpha14 NK T cells with the CD1d-restricted ligand alpha-galactosylceramide (alpha-GC). EAE induced in wild-type C57BL/6 (B6) mice was not appreciably altered by injection of alpha-GC. However, EAE induced in IL-4 knockout mice and IFN-gamma knockout mice was enhanced or suppressed by alpha-GC, respectively. This indicates that the IL-4 and IFN-gamma triggered by alpha-GC may play an inhibitory or enhancing role in the regulation of EAE. We next studied whether NK T cells of wild-type mice may switch their Th0-like phenotype toward Th1 or Th2. Notably, in the presence of blocking B7.2 (CD86) mAb, alpha-GC stimulation could bias the cytokine profile of NK T cells toward Th2, whereas presentation of alpha-GC by CD40-activated APC induced a Th1 shift of NK T cells. Furthermore, transfer of the alpha-GC-pulsed APC preparations suppressed or enhanced EAE according to their ability to polarize NK T cells toward Th2 or Th1 in vitro. These results have important implications for understanding the role of NK T cells in autoimmunity and for designing a therapeutic strategy targeting NK T cells.
Pál
E
E
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Tabira
T
T
Kawano
T
T
Taniguchi
M
M
Miyake
S
S
Yamamura
T
T
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005699:Galactosylceramides / Q000008:administration & dosage / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D018984:Epitopes, T-Lymphocyte; D005699:Galactosylceramides; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008024:Ligands; D008562:Membrane Glycoproteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016693:Receptors, Antigen, T-Cell, alpha-beta