Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation
Gurumoorthy Krishnamoorthy, … , Hartmut Wekerle, Andreas Holz
Gurumoorthy Krishnamoorthy, … , Hartmut Wekerle, Andreas Holz
Published September 1, 2006
Citation Information: J Clin Invest. 2006;116(9):2385-2392. https://doi.org/10.1172/JCI28330.
View: Text | PDF
Research Article Autoimmunity

Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation

Abstract

We describe a double-transgenic mouse strain (opticospinal EAE [OSE] mouse) that spontaneously develops an EAE-like neurological syndrome closely resembling a human variant of multiple sclerosis, Devic disease (also called neuromyelitis optica). Like in Devic disease, the inflammatory, demyelinating lesions were located in the optic nerve and spinal cord, sparing brain and cerebellum, and the murine lesions showed histological similarity with their human correlates. OSE mice have recombination-competent immune cells expressing a TCR-αβ specific for myelin oligodendrocyte glycoprotein (MOG) aa 35–55 peptide in the context of I-Ab along with an Ig J region replaced by the recombined heavy chain of a monoclonal antibody binding to a conformational epitope on MOG. OSE mouse B cells bound even high dilutions of recombinant MOG, but not MOG peptide, and processed and presented it to autologous T cells. In addition, in OSE mice, but not in single-transgenic parental mice, anti-MOG antibodies were switched from IgM to IgG1.

Authors

Gurumoorthy Krishnamoorthy, Hans Lassmann, Hartmut Wekerle, Andreas Holz

×

Figure 5

Enhanced autoreactivity of lymphocytes from OSE mice to rMOG.

Options: View larger image (or click on image) Download as PowerPoint
Enhanced autoreactivity of lymphocytes from OSE mice to rMOG. (A and B) ...
(A and B) Proliferation of splenocytes from OSE, TCRMOG single-transgenic, and IgHMOG single-transgenic mice in response to increasing concentrations of (A) rMOG and (B) MOG aa 35–55 peptide. (C) Proliferation of CD4+ T cells and B cells isolated from IgHMOG and TCRMOG single-transgenic mice that were combined as indicated after their purification (>90% purity) and stimulated with increasing amounts of rMOG. Note that the combination of MOG-reactive T and B cells caused a substantial increase in proliferation in response to rMOG, comparable to that of OSE splenocytes. (D) Splenocytes from an OSE mouse were labeled with CFSE and stimulated with optimal concentrations of rMOG in vitro. The dilution of cellular CFSE due to proliferation of live-gated CD4+CD3+ T lymphocytes (top) and live-gated CD19+ B lymphocytes (bottom) is shown. Splenocytes that remained without stimulus are represented by dotted lines. In A–C, each data point was run in triplicate, and error bars indicate SEM. Experiments in A and B were replicated on multiple occasions (>10), those in C and D were repeated twice.