Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/281226
- author
- Jahng, A ; Maricic, I ; Aguilera, C ; Cardell, Susanna LU ; Halder, RC and Kumar, V
- organization
- publishing date
- 2004
- 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
- 2016-04-01 16:07:57
- date last changed
- 2022-03-07 03:44:31
@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}}, keywords = {{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}}, doi = {{10.1084/jem.20031389}}, volume = {{199}}, year = {{2004}}, }