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 Vα14+ NK T cells, and a panel of Vα3/Vα8+ 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-γ 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.
Skip Nav Destination
Article navigation
5 April 2004
Article|
March 29 2004
Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide
Alex Jahng,
Alex Jahng
1La Jolla Institute for Allergy and Immunology (LIAI),
Search for other works by this author on:
Igor Maricic,
Igor Maricic
1La Jolla Institute for Allergy and Immunology (LIAI),
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Search for other works by this author on:
Carlos Aguilera,
Carlos Aguilera
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Search for other works by this author on:
Susanna Cardell,
Susanna Cardell
3Lund University, 221 00 Lund, Sweden
Search for other works by this author on:
Ramesh C. Halder,
Ramesh C. Halder
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Search for other works by this author on:
Vipin Kumar
Vipin Kumar
1La Jolla Institute for Allergy and Immunology (LIAI),
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Search for other works by this author on:
Alex Jahng
1La Jolla Institute for Allergy and Immunology (LIAI),
Igor Maricic
1La Jolla Institute for Allergy and Immunology (LIAI),
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Carlos Aguilera
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Susanna Cardell
3Lund University, 221 00 Lund, Sweden
Ramesh C. Halder
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
Vipin Kumar
1La Jolla Institute for Allergy and Immunology (LIAI),
2Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies (TPIMS), San Diego, CA 92121
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: [email protected]
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.
Received:
August 13 2003
Accepted:
February 23 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2004
J Exp Med (2004) 199 (7): 947–957.
Article history
Received:
August 13 2003
Accepted:
February 23 2004
Citation
Alex Jahng, Igor Maricic, Carlos Aguilera, Susanna Cardell, Ramesh C. Halder, Vipin Kumar; Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide . J Exp Med 5 April 2004; 199 (7): 947–957. doi: https://doi.org/10.1084/jem.20031389
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement