PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF INSULIN-DEPENDENT DIABETIC-PATIENTS RESPOND TO MULTIPLE ISLET-CELL PROTEINS

Insulin-dependent diabetes (IDDM) results from autoimmune destruction of pancreatic beta cells mediated predominately by cellular effector m echanisms, To date, investigators have studied a limited number of isl et cell proteins stimulatory to T cells, However, before development o f clinical IDDM, the majority of the beta cells are impaired or destro yed, Thus, numerous proteins from lysed beta cells would be accessible to the immune system of the patient, Our goal was to investigate the PBMC reactivity of IDDM patients to the full spectrum of fractionated human pancreatic islet cell proteins to determine whether numerous isl et cell proteins or a select few would be recognized, We observed that PBMCs From IDDM patients responded reproducibly (mean stimulation ind ex, >2.0) to the proteins in all m.w. regions, whereas the mean stimul ation index for controls from all m.w. regions was <2.0. Using three d ifferent islet protein preparations, PBMC responses of IDDM patients ( n = 30) and controls (n = 39) to the islet cell proteins were signific antly different, Dose responses were also demonstrated for the lymphoc yte reactivity of the IDDM patients (n = 29) vs controls (n = 56) to t he islet cell preparations, Proteins, presumably irrelevant to the IDD M disease process, from a human osteosarcoma cell line and normal huma n spleen cells did not stimulate PBMCs from IDDM patients or controls, Moreover, IDDM patients and controls responded similarly to mitogens and tetanus toroid, These studies show that at the time of diagnosis o f IDDM, PBMCs from IDDM patients are stimulated by a wide array of isl et cell proteins.