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

2003 ◽  
Vol 197 (9) ◽  
pp. 1073-1081 ◽  
Author(s):  
Estelle Bettelli ◽  
Maria Pagany ◽  
Howard L. Weiner ◽  
Christopher Linington ◽  
Raymond A. Sobel ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Disease ◽  
Transgenic Mice ◽  
Optic Neuritis ◽  
T Cell Receptor ◽  
Clinical Manifestations ◽  
Cell Receptor ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
The Central Nervous System ◽  
Target Autoantigen

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.

scholarly journals T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice.

1994 ◽  
Vol 179 (5) ◽  
pp. 1659-1664 ◽  
Author(s):  
V K Kuchroo ◽  
M Collins ◽  
A al-Sabbagh ◽  
R A Sobel ◽  
M J Whitters ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Disease ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Proteolipid Protein ◽  
Cell Receptor ◽  
Myelin Proteins ◽  
Laboratory Animals ◽  
Cell Repertoire ◽  
Tcr Repertoire

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced in laboratory animals by immunization with the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the role of the T cell receptor (TCR) repertoire in susceptibility to EAE induced by these two autoantigens. Autoreactive T cells induced after immunization with MBP use a limited set of TCR. In contrast, we demonstrate that T cell clones that recognize the encephalitogenic PLP epitope (PLP 139-151) use diverse TCR genes. When the TCR repertoire is limited by introduction of a novel rearranged TCR V beta 8.2 chain in transgenic SJL mice, EAE could be induced in the transgenic mice by immunization with the encephalitogenic epitopes of PLP, but not with the encephalitogenic epitope of MBP. Thus, skewing the TCR repertoire affects the susceptibility to EAE by immunization with MBP but not with PLP. These data demonstrate the biological consequences of the usage of a more diverse T cell repertoire in the development of an autoimmune disease.

T cell receptors in autoimmune disease as targets for immune intervention

Genome ◽  
1989 ◽  
Vol 31 (2) ◽  
pp. 656-661 ◽  
Author(s):  
Hans Acha-Orbea ◽  
L. Steinman ◽  
H. O. McDevitt
Keyword(s):  
T Cell ◽  
Autoimmune Disease ◽  
T Cell Receptor ◽  
Experimental Allergic Encephalomyelitis ◽  
Antibody Therapy ◽  
Cell Receptor ◽  
Allergic Encephalomyelitis ◽  
Immune Intervention ◽  
Receptor Antibodies ◽  
Experimental Allergic

The optimal form of treatment for an autoimmune disease should be highly specific, have few side effects, and allow treatment of clinically apparent disease. One target that could fulfill these requirements is the T cell receptor. To answer the question whether treatment of autoimmune disesase is possible with anti-T cell receptor antibodies, the heterogeneity of T cell receptor elements utilized in the T cell mediated autoimmune disease experimental allergic encephalomyelitis was analyzed. The limited heterogeneity of these elements allowed prevention and treatment of clinical autoimmune disease with anti-T cell receptor monoclonal antibodies. These results and their potential value for other autoimmune diseases are discussed.Key words: T cell receptor, autoimmune disease, monoclonal antibody therapy, experimental allergic encephalomyelitis.

scholarly journals CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer

2002 ◽  
Vol 196 (4) ◽  
pp. 481-492 ◽  
Author(s):  
Kristin V. Tarbell ◽  
Mark Lee ◽  
Erik Ranheim ◽  
Cheng Chi Chao ◽  
Maija Sanna ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Glutamic Acid Decarboxylase ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Acid Decarboxylase ◽  
Gad 65

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286–300 (p286) of GAD65. These mice have GAD65-specific CD4+ T cells, as shown by staining with an I-Ag7(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-10 when stimulated in vitro with GAD65 peptide 286–300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4+ T cells, or p286-tetramer+CD4+ Tcells, from GAD65 286–300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286–300-specific T cells have disease protective capacity and are not pathogenic.

Expression of a hybrid immunoglobulin-T cell receptor protein in transgenic mice

Cell ◽  
1989 ◽  
Vol 58 (5) ◽  
pp. 911-921 ◽  
Author(s):  
Michael L.B. Becker ◽  
Richard Near ◽  
Meredith Mudgett-Hunter ◽  
Michael N. Margolies ◽  
Ralph T. Kubo ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Protein

scholarly journals Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling

Brain ◽  
2010 ◽  
Vol 133 (2) ◽  
pp. 375-388 ◽  
Author(s):  
Wei Hu ◽  
Stefan Nessler ◽  
Bernhard Hemmer ◽  
Todd N. Eagar ◽  
Lawrence P. Kane ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Autoimmune Disease ◽  
Prion Protein ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signalling
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