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Vra4 congenic rats with allelic differences in the class II transactivator gene display altered susceptibility to experimental autoimmune encephalomyelitis

Harnesk, Karin; Swanberg, Maria LU ; Ockinger, Johan; Diez, Margarita; Lidman, Olle; Wallström, Erik; Lobell, Anna; Olsson, Tomas and Piehl, Fredrik (2008) In Journal of immunology (Baltimore, Md. : 1950) 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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publishing date
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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 (Baltimore, Md. : 1950)
volume
180
issue
5
pages
8 pages
publisher
American Association of Immunologists
external identifiers
  • 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
2017-08-06 05:18:09
@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},
  keyword      = {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 (Baltimore, Md. : 1950)},
  title        = {Vra4 congenic rats with allelic differences in the class II transactivator gene display altered susceptibility to experimental autoimmune encephalomyelitis},
  volume       = {180},
  year         = {2008},
}