Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus

Inclusion Criteria: * Type 1 Diabetes * Metabolic lability/instability characterized by hypoglycemia or ketoacidosis(\>2 hospital admissions in the previous year), erratic glucose profiles(MAGE \>120mg/dL), or disruption in lifestyle(danger to life, self or others). Reduced awareness of hypoglycemia or \> 1 episode in the last 1.5 years of severe hypoglycemia. * Persistently poor glucose control (as defined by HgbA1c\>10% at the end of six months of intensive management efforts with diabetes care team. * Progressive secondary complications as defined by * a new diagnosis by an ophthalmologist of proliferative retinopathy or clinically significant macular edema or therapy with photocoagulation during the last year; or * urinary albumin excretion rate \>300mg/day but proteinuria \<3g/day; or * symptomatic autonomic neuropathy (as defined by postural hypotension in the setting of euvolemia, gastroparesis or diarrhea attributed to diabetic neuropathy, or neuropathic bladder as diagnosed by an urologist) Exclusion Criteria: * Patient weighs more than 80kg or body mass index BMI\>28 * Patient's insulin requirement is \>55 Units/day. * Current use of immunosuppressive agents. * History of malignancy within 10 years (except for adequately treated basal or squamous cell CA of the skin). * Active peptic ulcer disease. * Severe unremitting diarrhea or other GI disorders potentially interfering with the ability to absorb oral medications. * Untreated proliferative retinopathy. * Pregnancy or breastfeeding. * Female subjects not post-menopausal or surgically sterile, or not using an acceptable method or contraception. * Active infections. * Major ongoing psychiatric illness. * Ongoing substance abuse, drug or alcohol; or recent history of noncompliance. * Portal hypertension or history of significant liver disease. * Lymphopenia (\<1000/ul) or leukopenia (\<3000 total leukocytes/ul) or an absolute CD4 count \<500/ul. * Presence or history of panel-reactive anti-HLA antibody \>20%. * Evidence of acute EBV infection (IgM\>IgG) OR no serologic evidence of previous exposure to EBV (IgG\>IgM). * Serologic evidence of infection with HIV or HbsAg or HCV Ab positive. * Creatinine clearance \<60ml/min/m2. * Positive lymphocytoxic cross-match using donor lymphocytes and serum