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Detection of cell-mediated immunity in type I diabetes mellitus
F Calcinaro1, L Hao, H P Chase
1Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
Type I insulin dependent diabetes mellitus (IDDM) is thought to result from chronic, cell-mediated, 'autoimmune' islet damage. Antibody testing is extensively used to define and follow the pre-diabetic population. However, the assay for cell mediated immunity (CMI) should be more predictive of impending disease. This report shows that it is possible to detect human islet reactive CMI in the IDDM patient. Groups of athymic CD-1 nu/nu mice were injected intraperitoneally with either mononuclear blood cells (MBCs) or plasma from 10 newly diagnosed Type I diabetic patients and 10 normal control subjects. Both glycemic control and histopathology were used to assay islet specific CMI in diabetic individuals. None of the injected mice showed any impairment of glycemic control. However, MBCs from six of 10 diabetic patients, but from none of the 10 normal subjects, induced significant mononuclear cell infiltrate in the pancreas of the recipient mice (P = 0.005). The infiltrate was focused on the islet tissue and no damage was seen in control tissues. No histological abnormalities were observed when plasma was transferred. We conclude that cellular reactivity seen in this model is tissue specific and disease associated. Our findings provide evidence that CMI to human islet tissue can be detected in IDDM patients.