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Published online 29 March 2004 doi:10.1084/jem.20031389
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 7, 947-957
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Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide

Alex Jahng1, Igor Maricic1,2, Carlos Aguilera2, Susanna Cardell3, Ramesh C. Halder2, and Vipin Kumar1,2

1 La Jolla Institute for Allergy and Immunology (LIAI), and 2 Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
3 Lund University, 221 00 Lund, Sweden

Address correspondence to Vipin Kumar, Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Ct., San Diego, CA 92121. Phone: (858) 455-3870; Fax: (858) 455-3804; email: Vkumar{at}tpims.org

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 V{alpha}14+ NK T cells, and a panel of V{alpha}3/V{alpha}8+ 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.

Key Words: sulfatides • CD1d • EAE • NK T cells • glycolipids

Abbreviations used in this paper: CGT, UDP-galactose ceramide galactosyltransferase; CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; GalCer, galactosyl ceramide; MBP, myelin basic protein; MS, multiple sclerosis.


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