Vra4 congenic rats with allelic differences in the class II transactivator gene display altered susceptibility to experimental autoimmune encephalomyelitis
(2008) In Journal of immunology 180(5). p.96-3289- Abstract
Presentation of Ag bound to MHC class II (MHC II) molecules to CD4+ T cells is a key event in adaptive immune responses. Genetic differences in MHC II expression in the rat CNS were recently positioned to allelic variability in the CIITA gene (Mhc2ta), located within the Vra4 locus on rat chromosome 10. In this study, we have examined reciprocal Vra4-congenic strains on the DA and PVGav1 backgrounds, respectively. After experimental nerve injury the strain-specific MHC II expression on microglia was reversed in the congenic strains. Similar findings were obtained after intraparenchymal injection of IFN-gamma in the brain. Expression of MHC class II was also lower on B cells and dendritic cells from the DA.PVGav1-Vra4- congenic strain... (More)
Presentation of Ag bound to MHC class II (MHC II) molecules to CD4+ T cells is a key event in adaptive immune responses. Genetic differences in MHC II expression in the rat CNS were recently positioned to allelic variability in the CIITA gene (Mhc2ta), located within the Vra4 locus on rat chromosome 10. In this study, we have examined reciprocal Vra4-congenic strains on the DA and PVGav1 backgrounds, respectively. After experimental nerve injury the strain-specific MHC II expression on microglia was reversed in the congenic strains. Similar findings were obtained after intraparenchymal injection of IFN-gamma in the brain. Expression of MHC class II was also lower on B cells and dendritic cells from the DA.PVGav1-Vra4- congenic strain compared with DA rats after in vitro stimulation with IFN-gamma. We next explored whether Vra4 may affect the outcome of experimental autoimmune disease. In experimental autoimmune encephalomyelitis induced by immunization with myelin oligodendrocyte glycoprotein, DA.PVGav1-Vra4 rats displayed a lower disease incidence and milder disease course compared with DA, whereas both PVGav1 and PVGav1.DA-Vra4 rats were completely protected. These results demonstrate that naturally occurring allelic differences in Mhc2ta have profound effects on the quantity of MHC II expression in the CNS and on immune cells and that this genetic variability also modulates susceptibility to autoimmune neuroinflammation.
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- author
- Harnesk, Karin ; Swanberg, Maria LU ; Ockinger, Johan ; Diez, Margarita ; Lidman, Olle ; Wallström, Erik ; Lobell, Anna ; Olsson, Tomas and Piehl, Fredrik
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- keywords
- Alleles, Animals, Animals, Congenic, Cells, Cultured, Down-Regulation, Encephalomyelitis, Autoimmune, Experimental, Female, Genetic Markers, Genetic Predisposition to Disease, Histocompatibility Antigens Class II, Male, Neurogenic Inflammation, Nuclear Proteins, Rats, Rats, Inbred Strains, Rhizotomy, Spinal Nerve Roots, Trans-Activators, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- in
- Journal of immunology
- volume
- 180
- issue
- 5
- pages
- 8 pages
- publisher
- American Association of Immunologists
- external identifiers
-
- pmid:18292553
- scopus:49149123166
- ISSN
- 0022-1767
- language
- English
- LU publication?
- no
- id
- 42d151ee-c51c-43eb-98d7-3e09977676ad
- date added to LUP
- 2017-02-22 09:43:39
- date last changed
- 2024-01-13 15:04:26
@article{42d151ee-c51c-43eb-98d7-3e09977676ad,
abstract = {{<p>Presentation of Ag bound to MHC class II (MHC II) molecules to CD4+ T cells is a key event in adaptive immune responses. Genetic differences in MHC II expression in the rat CNS were recently positioned to allelic variability in the CIITA gene (Mhc2ta), located within the Vra4 locus on rat chromosome 10. In this study, we have examined reciprocal Vra4-congenic strains on the DA and PVGav1 backgrounds, respectively. After experimental nerve injury the strain-specific MHC II expression on microglia was reversed in the congenic strains. Similar findings were obtained after intraparenchymal injection of IFN-gamma in the brain. Expression of MHC class II was also lower on B cells and dendritic cells from the DA.PVGav1-Vra4- congenic strain compared with DA rats after in vitro stimulation with IFN-gamma. We next explored whether Vra4 may affect the outcome of experimental autoimmune disease. In experimental autoimmune encephalomyelitis induced by immunization with myelin oligodendrocyte glycoprotein, DA.PVGav1-Vra4 rats displayed a lower disease incidence and milder disease course compared with DA, whereas both PVGav1 and PVGav1.DA-Vra4 rats were completely protected. These results demonstrate that naturally occurring allelic differences in Mhc2ta have profound effects on the quantity of MHC II expression in the CNS and on immune cells and that this genetic variability also modulates susceptibility to autoimmune neuroinflammation.</p>}},
author = {{Harnesk, Karin and Swanberg, Maria and Ockinger, Johan and Diez, Margarita and Lidman, Olle and Wallström, Erik and Lobell, Anna and Olsson, Tomas and Piehl, Fredrik}},
issn = {{0022-1767}},
keywords = {{Alleles; Animals; Animals, Congenic; Cells, Cultured; Down-Regulation; Encephalomyelitis, Autoimmune, Experimental; Female; Genetic Markers; Genetic Predisposition to Disease; Histocompatibility Antigens Class II; Male; Neurogenic Inflammation; Nuclear Proteins; Rats; Rats, Inbred Strains; Rhizotomy; Spinal Nerve Roots; Trans-Activators; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
number = {{5}},
pages = {{96--3289}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
title = {{Vra4 congenic rats with allelic differences in the class II transactivator gene display altered susceptibility to experimental autoimmune encephalomyelitis}},
volume = {{180}},
year = {{2008}},
}