Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice.
Although deficiencies in the NKT cell population have been observed in multiple sclerosis and mouse strains susceptible to experimental autoimmune encephalomyelitis (EAE), little is known about the function of these cells in CNS autoimmunity. In this work we report that TCR Valpha14-Jalpha281 transgenic nonobese diabetic mice, which are enriched in CD1d-restricted NKT cells, are protected from EAE. The protection is associated with a striking inhibition of Ag-specific IFN-gamma production in the spleen, implying modulation of the encephalitogenic Th1 response. This modulation is independent of IL-4 because IL-4-deficient Valpha14-Jalpha281 mice are still protected against EAE and independent of NKT cell-driven Th1 to Th2 deviation, because no increased autoantigen-specific Th2 response was observed in immunized Valpha14-Jalpha281 transgenic mice. Our findings indicate that enrichment and/or stimulation of CD1d-dependent NKT cells may be used as a novel strategy to treat CNS autoimmunity.
Mars
Lennart T
LT
Institut National de la Santé et de la Recherche Médicale, Unité 546, Hôpital Pitié-Salpetriere, Paris, France.
Laloux
Véronique
V
Goude
Karine
K
Desbois
Sabine
S
Saoudi
Abdelhadi
A
Van Kaer
Luc
L
Lassmann
Hans
H
Herbelin
André
A
Lehuen
Agnès
A
Liblau
Roland S
RS
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C445081:myelin oligodendrocyte glycoprotein (35-55); D015847:Interleukin-4; D007371:Interferon-gamma