Bm. Brooksworrell et al., PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF INSULIN-DEPENDENT DIABETIC-PATIENTS RESPOND TO MULTIPLE ISLET-CELL PROTEINS, The Journal of immunology, 157(12), 1996, pp. 5668-5674
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.