Research Program:

The major thrust of our research is directed toward the understanding of mechanisms of pathogenesis and regulation of autoimmune diabetes in the NOD mouse. Our tools for this research are a panel of islet-specific diabetogenic T cell clones and several NOD mouse strain variations, including the diabetes-resistant NOR strain, diabetes-resistant NOD congenics, the NOD-scid, and a TCR transgenic mouse on the NOD background. One important project is to isolate and identify the beta cell antigen(s) for the pathogenic T cell clones we have produced. A second project is the comprehensive analysis of requirements for disease induction by T cell clones and how to inhibit this process. A third project is to investigate regulatory mechanisms in the NOD mouse and to isolate regulatory T cell clones. In addition to these long-term projects, we have recently been exploring some new research directions, including the encapsulation of islets for transplantion and the role of oxidative stress in type 1 diabetes.

Bibliography

• Haskins K, McDuffie M. (1990) Acceleration of Diabetes in Young NOD Mice with a CD4+ Islet-Specific T Cell Clone. Science 249:1433.
• Bergman B, Haskins K. (1994) Islet-specific T cell Clones from the NOD Mouse Respond to Beta Granule Antigen.Diabetes 43:197.
• Bergman B, Haskins K. (1997) Autoreactive T Cell Clones from the Nonobese Diabetic (NOD) Mouse. Proceedings of the Society for Experimental Biology and Medicine 214:41
• Stratmann, T., Martin-Orozco, N., Mallet-Designe, V., Poirot, L., McGavern, D., Losyev, G., Dobbs, C.M., Oldstone, M.B.A., Yoshida, K., Kikutani, H., Mathis, D., Benoist, C., Haskins, K. and Teyton, L. 2003. Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity. J. Clin. Invest. 112: 902.
• Haskins, K., Bradley, B., Powers, K., Fadok, V., Flores, S., Ling, X., Pugazhenthi, S., Reusch, J. and Kench, J. 2003. Oxidative stress in type 1 diabetes. In Immunology of Diabetes II, Pathogenesis from Mouse to Man (C.B. Sanjeevi, G.S. Eisenbarth, eds.) Ann. N.Y. Acad. Sci. 1005: 43-54.
• Haskins, K. T-cell receptor transgenic (TCR-Tg) mice from two diabetogenic CD4+ islet-antigen-specific T-cell clones. 2004. J. Autoimmunity. In Press.
• Pauza, M., Dobbs, C. M., He, J., Patterson, T., Wagner, S., Anobile, B., Bradley, B., Lo, D. and Haskins, K. 2004. Absence of autoantigen in a T cell receptor transgenic NOD mouse: a flexible model of type 1 diabetes. Diabetes. In Press.

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