Myelin Oligodendrocyte Glycoprotein–specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis

By E. Bettelli, M. Pagany, Howard L. Weiner, C. Linington, R. Sobel, V. Kuchroo. Journal of Experimental Medicine, 2003

853 citations recorded by the source corpus.

Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.

Subfields: Immunology, Neurology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/86f67e524c1b14bdd6ff61b6b3a54929b94172db

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. V. Kuchroo
2. D. Cua
3. Arlene H. Sharpe
4. G. Freeman
5. T. Korn
6. Loise M. Francisco
7. M. Oukka
8. E. Bettelli

In Neurology

1. Hans Lassmann
2. U. Hanisch
3. M. Simons
4. Michael T. Heneka
5. G. Moalem-Taylor
6. P. Austin
7. M. O’Banion
8. J. Lladó

In Pathology and Forensic Medicine

1. Hans Lassmann
2. V. Kuchroo
3. T. Korn
4. E. Bettelli
5. M. Oukka
6. D. Cua

Citations in the corpus

• Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. (2006, background): “…of EAE been developed, but even these are dependent on the use of transgenic approaches to override the intrinsic regulatory mechanisms that normally suppress tissue-specific autoaggression (Waldner et al., 2000; Bettelli et al., 2003; Zehntner et al., 2003; T. Hünig and R. Gold, in preparation).”
• Immunology of multiple sclerosis. (2005, neutral): “Optic neuritis is also seen in MOG-induced EAE in DA rats (102), and the relatively higher expression of MOG in the optic nerve has been proposed as one explanation for the involvement of the optic nerve (138).”
• Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis (2011, methodology): “…then gently washed twice with DMEM containing 10% FCS. Myelin oligodendrocyte glycoprotein (MOG)-specific CD4+ T cells were isolated from TCR-transgenic 2D2 mice (Bettelli et al., 2003) by negative selection using magnetic beads (R&D Systems) as previously described (Krishnamoorthy et al., 2006).”
• PD-L1 regulates the development, maintenance, and function of induced regulatory T cells (2009, methodology): “GFP; Bettelli et al., 2006) were generated in our laboratory by crossing 2D2 TCR Tg mice (Bettelli et al., 2003) with Foxp3.”
• Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation (2007, background): “In contrast, MOG-primed Foxp3/GFP + T cells were effective in suppressing the MOG 35–55 -specific proliferation of naive 2D2 responder T cell”
• Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. (2008, neutral): “org Volume 118 Number 10 October 2008 The effects of B cell depletion on antigen-specific T cell proliferation in vivo were also assessed by the adoptive transfer of CFSElabeled CD4+ T cells from TCRMOG mice (36) on day 17.”
• CNS immune privilege: hiding in plain sight (2006, background): “Nearly 20 years ago, Hickey and Kimura (74) used irradiation chimeric rats to differentially manipulate the ability of either resident parenchymal microglial or the bone-marrow-derived cells to express the appropriate MHC class II to act as APCs in MBP-induced EAE (Fig.”
• Fate mapping of interleukin 17-producing T cells in inflammatory responses (2011, methodology): “To optimize cell yield and adoptive transfer, we used reporter mice with transgenic expression of the 2D2 TCR specific for MO”