EVIDENCE FOR SUPERANTIGEN INVOLVEMENT IN INSULIN-DEPENDENT DIABETES-MELLITUS ETIOLOGY

INSULIN-DEPENDENT diabetes mellitus (IDDM) is a T-cell-mediated autoim mune disease whose onset is believed to be triggered by unknown enviro nmental factors acting on a predisposing genetic background. Islet-inf iltrating T (IIT) cells from two IDDM patients, who had died at the on set of the disease from brain swelling as a complication of ketoacidos is, were analysed. The results provided evidence for the involvement o f a pancreatic islet cell membrane-bound superantigen(1,2) as a diabet es aetiopathogenetic factor. There was a selective expansion of a T-ce ll receptor (TCR) variable segment of the beta-chain (V beta 7) in the se IIT cells in association with unselected V alpha-chain segments; ex tensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7(+) T-cell clones among peripheral blood lymp hocytes from non-diabetic individuals.