OBJECTIVEIslet autoimmunity has long been recognized in the pathogenesis of type 1 diabetes and is becoming increasingly acknowledged as a component in the pathogenesis of type 2 diabetes. Islet reactive T cells and autoantibodies have been demonstrated in type 1 diabetes, whereas islet autoimmunity in type 2 diabetes has been limited to islet autoantibodies. In this study, we investigated whether islet reactive T cells might also be present in type 2 diabetic patients and how islet reactive T cells correlate with β-cell function.RESEARCH DESIGN AND METHODSAdult phenotypic type 2 diabetic patients (n = 36) were screened for islet reactive T-cell responses using cellular immunoblotting and five islet autoantibodies (islet cell antibody, GADA, insulin autoantibody, insulinoma-associated protein-2 autoantibody, and zinc transporter autoantibody).RESULTSWe identified four subgroups of adult phenotypic type 2 diabetic patients based on their immunological status (Ab−T−, Ab+T−, Ab−T+, and Ab+T+). The Ab−T+ type 2 diabetic patients demonstrated T-cell responses similar to those of the Ab+T+ type 2 diabetic patients. Data were adjusted for BMI, insulin resistance, and duration of diabetes. Significant differences (P < 0.02) were observed among groups for fasting and glucagon-stimulated C-peptide responses. T-cell responses to islet proteins were also demonstrated to fluctuate less than autoantibody responses.CONCLUSIONSWe have identified a group of adult autoimmune phenotypic type 2 diabetic patients who are Ab−T+ and thus would not be detected using autoantibody testing alone. We conclude that islet autoimmunity may be more prevalent in adult phenotypic type 2 diabetic patients than previously estimated.

clinicaltrials.gov Identifier: NCT00821964.

This Phase I study evaluated the feasibility of expanding HER-2/neu (HER2) vaccine-primed peripheral blood T-cells ex vivo and assessed the safety of T-cell infusions. Eight patients with HER2 + treatment refractory metastatic cancers were enrolled. T-cells could be expanded to predefined parameters in 7 patients (88%). Ninety-two percent of adverse events were grades 1 or 2. Three of 7 patients developed infusion related inflammatory reactions at their disease sites. HER2 specific T-cells significantly increased in vivo compared to pre-infusion levels (p=0.010) and persisted in 4/6 patients (66%) over 70 days after the first infusion. Partial clinical responses were observed in 43% of patients. Levels of T-regulatory cells in peripheral blood prior to infusion (p<0.001), the level of HER2 specific T-cells in vivo (p=0.030), and development of diverse clonal T-cell populations (p<0.001) were associated with response. The generation of HER2 vaccine primed autologous T-cells for therapeutic infusion is feasible and well tolerated. This approach provides a foundation for the application of T-cell therapy to additional solid tumor types.