The Oshima Lab is involved in the study of immunosuppression of autoimmune disease and disease mechanisms involving auto-reactive T cells in autoimmunity.
Autoimmune diseases result from immune responses of a host immune system to self antigens (Ags). Production of disease-causing auto-antibodies (Abs) in most autoimmune diseases depends on auto-reactive T cells that recognize the epitopes of the pathogenic Ags in the context of MHC class II molecules.
Immunosuppression of Autoimmune Disease by Targeting MHC
There has been growing evidence showing that certain HLA alleles are associated with autoimmune disease. Inhibition of the Ag-presenting function of disease-related MHC class II alleles could lead to a regression of the auto-reactive T cell population. To prove this hypothesis, we used as a disease model myasthenia gravis (MG), in which acetylcholine receptor (AChR) is its major autoAg. We prepared mAbs against Ag-binding region of mouse MHC and various HLA DQ alleles that are disease-associated. We then tested their efficacy in vivo using a mouse model of MG, and in vitro using live AChR-specific T cells from patients with MG. Interim findings have been published.
Investigation of the Role of Auto-Reactive T cells in the Pathogenesis of Autoimmune Disease
In MG, collaboration between T- and B-cells that recognize distinctive disease-associated regions of AChR ß-chain is responsible for the production of disease-causing Abs. We have identified T-cell epitope regions recognized by peripheral blood lymphocytes from a set of MG patients, and analyzed their responses in the presentation by HLA DQ allele types. Interim findings have been published. B-cell epitope regions that may have specific association with particular HLA alleles are currently under investigation by using samples from the same set of patients.
Determination of MHC Class II-Restricted Pathogenic Epitope Regions of Autoantigen in Autoimmune Disease
Investigation on disease mechanism and/or treatment strategy of MG depends on the animal study using an animal (mouse) model of MG, termed experimental autoimmune MG (EAMG). There is a need to improve current protocol for induction of disease in a disease-susceptible mouse strain. Development of an efficient protocol for induction of mouse EAMG by using additional adjuvant is under investigation.
Development of Improved Induction Methods for Experimental Autoimmune Disease.
Use of steroids in MG patients causes a decrease in their bone mass. However, B6 mice with induced clinical MG sometimes show weight loss, which might correlate with low bone mass. This might suggest that different process for reduction in bone mineral density might exist in the disease mechanism of MG. The study is underway with collaboration from bone research specialists in other institution.