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More MS news articles for March 2004

Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15051763

J Exp Med. 2004 Apr 5;199(7):947-57. Epub 2004 Mar 29
Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V.
Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Ct., San Diego, CA 92121

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.