The work in our laboratory involves translational studies in human immunology, focused on Type 1 diabetes. We are carrying out clinical studies of new immune therapies, in particular humanized anti-CD3 monoclonal antibody, and study the metabolic and immunologic effects of these interventions on the disease process. We are studying the ability of this intervention to prevent the loss of insulin production that characterizes the disease and determining the optimal approach to use this and other immune treatments in the disease setting. We have identified a novel regulatory mechanism that we believe is involved in the patients? response to anti-CD3 mAb and plan to expand these studies so that adoptive immune therapy can be performed without the need for systemic treatment of patients. In addition, we are interested in developing new ways in which immune therapies can be combined with cellular and/or metabolic approaches to restore normal beta cell mass and function. We are testing whether immune interventions can lead to spontaneous restoration of beta cell mass and developing new approaches to stimulate beta cell regeneration. Our studies to address this goal involve studies in patients and in animal models of the disease.

Sherry, N.A., Kushner, J.A., Glandt, M., Kitamura, T., Brillantes, A-M., and Herold, K.C. (In press). Effects of autoimmunity and immune therapy on beta cell turnover in Type 1 diabetes. Diabetes.

Herold, K.C., et al. (2005). A single course of anti-CD3 mAb hOKT3 gamma 1(Ala-Ala) results in improvement in insulin secretion and clinical parameters for at least 2 years after onset of Type 1 diabetes. Diabetes 54:1763-9.

Bisikirska, B., Colgan, J., Luban, J., Bluestone, J.A., and Herold, K.C. (2005). Human T cell receptor signaling with modified anti-CD3 monoclonal antibody expands CD8+ T cells and induces regulatory CD8+CD25+ cells. J. Clin Invest. 115:2904-2913.