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CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.

Teige, Anna LU ; Teige, Ingrid; Lavasani, Shahram LU ; Bockermann, Robert LU ; Mondoc, Emma LU ; Holmdahl, Rikard LU and Issazadeh-Navikas, Shohreh (2004) In Journal of Immunology 172(1). p.186-194
Abstract
The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1-/- mice develop a clinically more severe and chronic EAE compared with CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD1+/+ and CD1-/- mice but an amplified cytokine response in CD1-/-... (More)
The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1-/- mice develop a clinically more severe and chronic EAE compared with CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD1+/+ and CD1-/- mice but an amplified cytokine response in CD1-/- mice as measured by both the Th1 cytokine IFN-{gamma} and the Th2 cytokine IL-4. Investigation of cytokine production at the site of inflammation showed a CNS influx of TGF-{beta}1-producing cells early in the disease in CD1+/+ mice, which was absent in the CD1-/- mice. Passive transfer of EAE using an autoreactive T cell line induced equivalent disease in both groups, which suggested additional requirements for activation of the CD1-dependent regulatory pathway(s). When immunized with CFA before T cell transfer, the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-{beta}1 production and through limiting autoreactive T cell activation, but not necessarily via effects on the Th1/Th2 balance. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
172
issue
1
pages
186 - 194
publisher
American Association of Immunologists
external identifiers
  • pmid:14688325
  • wos:000187427700027
  • scopus:0346734191
ISSN
1550-6606
language
English
LU publication?
yes
id
06773b21-cf46-490c-b4fa-b7e7c40f3ac0 (old id 119488)
alternative location
http://www.jimmunol.org/cgi/content/abstract/172/1/186
date added to LUP
2007-06-26 13:12:16
date last changed
2017-01-01 06:51:12
@article{06773b21-cf46-490c-b4fa-b7e7c40f3ac0,
  abstract     = {The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1-/- mice develop a clinically more severe and chronic EAE compared with CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD1+/+ and CD1-/- mice but an amplified cytokine response in CD1-/- mice as measured by both the Th1 cytokine IFN-{gamma} and the Th2 cytokine IL-4. Investigation of cytokine production at the site of inflammation showed a CNS influx of TGF-{beta}1-producing cells early in the disease in CD1+/+ mice, which was absent in the CD1-/- mice. Passive transfer of EAE using an autoreactive T cell line induced equivalent disease in both groups, which suggested additional requirements for activation of the CD1-dependent regulatory pathway(s). When immunized with CFA before T cell transfer, the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-{beta}1 production and through limiting autoreactive T cell activation, but not necessarily via effects on the Th1/Th2 balance.},
  author       = {Teige, Anna and Teige, Ingrid and Lavasani, Shahram and Bockermann, Robert and Mondoc, Emma and Holmdahl, Rikard and Issazadeh-Navikas, Shohreh},
  issn         = {1550-6606},
  language     = {eng},
  number       = {1},
  pages        = {186--194},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.},
  volume       = {172},
  year         = {2004},
}