Toward a cure for type 1 diabetes mellitus: diabetes-suppressive dendritic cells and beyond

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Abstract
Insulin has been the gold standard therapy for diabetes since its discovery and commercial availability. It remains the only pharmacologic therapy for type 1 diabetes (T1D), an autoimmune disease in which autoreactive T cells specifically kill the insulin-producing beta cells. Nevertheless, not even molecularly produced insulin administered four or five times per day can provide a physiologic regulation able to prevent the complications that account for the morbidity and mortality of diabetic patients. Also, insulin does not eliminate the T1D hallmark: beta-cell-specific autoimmunity. In other words, insulin is not a 'cure'. A successful cure must meet the following criteria: (i) it must either replace or maintain the functional integrity of the natural, insulin-producing tissue, the endocrine islets of Langerhans' and, more specifically, the insulin-producing beta cells; (ii) it must, at least, control the autoimmunity or eliminate it altogether; and (iii) it must be easy to apply to a large number of patients. Criterion 1 has been partially realized by allogeneic islet transplantation. Criterion 2 has been partially realized using monoclonal antibodies specific for T-cell surface proteins. Criterion 3 has yet to be realized, given that most of the novel therapies are currently quasi-patient-specific. Herein, we outline the current status of non-insulin-based therapies for T1D, with a focus on cell-based immunomodulation which we propose can achieve all three criteria illustrated above.