Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide.
Class I and class II MHC-restricted T cells specific for proteins present in myelin have been shown to be involved in autoimmunity in the central nervous system (CNS). It is not yet known whether CD1d-restricted T cells reactive to myelin-derived lipids are present in the CNS and might be targeted to influence the course of autoimmune demyelination. Using specific glycolipid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1d. This population is distinct from the invariant Valpha14+ NK T cells, and a panel of Valpha3/Valpha8+ CD1d-restricted NK T cell hybridomas is unable to recognize sulfatide in the presence of CD1d+ antigen-presenting cells. Interestingly, during experimental autoimmune encephalomyelitis a model for human multiple sclerosis, sulfatide-reactive T cells but not invariant NK T cells are increased severalfold in CNS tissue. Moreover, treatment of mice with sulfatide prevents antigen-induced experimental autoimmune encephalomyelitis in wild-type but not in CD1d-deficient mice. Disease prevention correlates with the ability of sulfatide to suppress both interferon-gamma and interleukin-4 production by pathogenic myelin oligodendrocyte glycoprotein-reactive T cells. Since recognition of sulfatide by CD1d-restricted T cells has now been shown both in mice and humans, study of murine myelin lipid-reactive T cells may form a basis for the development of intervention strategies in human autoimmune demyelinating diseases.
Jahng
Alex
A
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Maricic
Igor
I
Aguilera
Carlos
C
Cardell
Susanna
S
Halder
Ramesh C
RC
Kumar
Vipin
V
D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D055610:Antigens, CD1d; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D015551:Autoimmunity; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology / Q000517:prevention & control; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013433:Sulfoglycosphingolipids / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D013433:Sulfoglycosphingolipids; D015847:Interleukin-4; D007371:Interferon-gamma