CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/119488
- author
- Teige, Anna LU ; Teige, Ingrid ; Lavasani, Shahram LU ; Bockermann, Robert LU ; Mondoc, Emma LU ; Holmdahl, Rikard LU and Issazadeh-Navikas, Shohreh
- organization
- publishing date
- 2004
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Animal Physiology (Closed 2011) (011011000), Functional Zoology (432112239), Immunology (013212020)
- 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
- 2016-04-01 15:56:44
- date last changed
- 2022-02-05 04:45:37
@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.}}, url = {{http://www.jimmunol.org/cgi/content/abstract/172/1/186}}, volume = {{172}}, year = {{2004}}, }