Recombinase-activating gene 1-associated expression of the myelin basic protein 1-11-specific transgenic T-cell receptor in H-2b mice.

We pursued a breeding strategy intended to generate disease-resistant mice with exclusive expression of the H-2(u)-restricted myelin basic protein (MBP) 1-11 peptide-specific transgenic (Tg) T-cell receptor (TCR) on the T-cell-deficient RAG1KO (H-2(b)) background. Utilizing specific screening assays for the offspring, analyses of the F1 intercross and subsequent crosses revealed that the TgTCR-associated clonotypic marker detected by the 3H12 mAb could be found only in association with the H-2(b) homozygous background in offspring possessing a functional rag1 gene. Moreover, expression of the MBP-specific TgTCR could not be found in H-2(b) homozygous offspring that were RAG1 deficient (rag1(-/-)).

Bone marrow lacking integrin expression facilitates an enhanced susceptibility to EAE in the xenogeneic bone marrow chimeras.

Xenotransplantation of rat bone marrow cells (BMC) into immunodeficient (SCID) mice generates chimeric mice susceptible to paralytic autoimmune CNS inflammation. Herein, we identified a disease relevant subset of transplantable BMC lacking expression of CD11b/c and CD49d. Moreover, disease susceptibility was enhanced in the presence of non-myelin specific T-cells.

A telemetric study of physiologic changes in mice with induced autoimmune encephalomyelitis.

Dysfunction of the autonomic nervous system may be an important component of disease progression in multiple sclerosis (MS), a paralytic inflammatory autoimmune disease of the central nervous system. Using the experimental autoimmune encephalomyelitis mouse model of MS, the authors carried out a pilot study to investigate whether telemetric monitoring might be a feasible approach for detecting disturbances in the autonomic control of heart rate and blood pressure after disease induction. Telemetric monitoring devices that were implanted in mice provided useful information regarding the physiologic changes that accompanied disease induction and progression.

Treatment of experimental autoimmune encephalomyelitis with alpha lipoic acid and associative conditioning.

We have initiated studies to evaluate the suitability of performing therapeutic conditioning trials in experimental autoimmune encephalomyelitis (EAE) mice treated with alpha lipoic acid (ALA). EAE was induced in SJL mice by active immunization with myelin antigen. Once daily subcutaneous injection of ALA served as the unconditional stimulus (US) administered with the conditional stimulus (CS) saccharin-flavored drinking water under a regimen of restricted water access.

Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis.

The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires.