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Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide

Jahng, A; Maricic, I; Aguilera, C; Cardell, Susanna LU ; Halder, RC and Kumar, V (2004) In Journal of Experimental Medicine 199(7). p.947-957
Abstract
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 glycohpid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1 d. 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... (More)
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 glycohpid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1 d. 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
glycolipids, NK T cells, EAE, sulfatides, CD1d
in
Journal of Experimental Medicine
volume
199
issue
7
pages
947 - 957
publisher
Rockefeller University Press
external identifiers
  • pmid:15051763
  • wos:000220761000007
  • scopus:1842682026
ISSN
1540-9538
DOI
10.1084/jem.20031389
language
English
LU publication?
yes
id
e4e067b6-2697-4369-838d-2514f31f49b6 (old id 281226)
date added to LUP
2007-10-23 10:26:34
date last changed
2017-12-10 04:30:41
@article{e4e067b6-2697-4369-838d-2514f31f49b6,
  abstract     = {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 glycohpid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1 d. 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.},
  author       = {Jahng, A and Maricic, I and Aguilera, C and Cardell, Susanna and Halder, RC and Kumar, V},
  issn         = {1540-9538},
  keyword      = {glycolipids,NK T cells,EAE,sulfatides,CD1d},
  language     = {eng},
  number       = {7},
  pages        = {947--957},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide},
  url          = {http://dx.doi.org/10.1084/jem.20031389},
  volume       = {199},
  year         = {2004},
}