Insulin-dependent diabetes mellitus (IDDM) results from a T-cell-mediated destruction of the insulin-producing β-cells. In this study, we designed a sensitive assay to detect and identify islet cell-reactive T-cells in patients with newly diagnosed IDDM. The relation between T-cell recognition of β-cell antigens with IDDM and the pathogenesis of the disease (the β-cell destruction process) was tested in a large group of IDDM patients and compared with T-cell responses in nondiabetic children with other chronic inflammations and in immunologically normal, age-matched control subjects. The results demonstrate that peripheral blood T-cells reacting with a β-cell membrane preparation enriched for insulin-secretory granule antigen were detectable in the majority of newly diagnosed IDDM patients (27 of 40 [67%]; mean stimulation index [SI] 37.0). Such reactivity was reduced postonset in IDDM patients proportionally to the duration of the disease (11 of 30 [37%]; mean SI 8.7). Nondiabetic age-matched control subjects showed no responses or moderate responses to the granule preparation (4 of 48 [8%]; mean SI 3.4). The magnitude of the T-cell response was significantly greater in newly diagnosed IDDM patients than in IDDM patients tested at least 2 years postonset (P < 0.001). Two children in remission for insulin dependency (so-called honeymoon period) displayed exceptionally high proliferative responses to insulin-secretory granules (mean SI 86.7). These results imply that T-cell recognition of insulin-secretory granule antigens is associated with IDDM and in particular with the immune-mediated process of β-cell destruction.
Skip Nav Destination
Article navigation
Original Articles|
March 01 1995
T-Cell Reactivity to β-Cell Membrane Antigens Associated With β-Cell Destruction in IDDM
Bart O Roep;
Bart O Roep
Department of Immunohaematology and Blood Bank, University Hospital Leiden
Leiden
Search for other works by this author on:
Aram A Kallan;
Aram A Kallan
Department of Immunohaematology and Blood Bank, University Hospital Leiden
Leiden
Search for other works by this author on:
Gaby Duinkerken;
Gaby Duinkerken
Department of Immunohaematology and Blood Bank, University Hospital Leiden
Leiden
Search for other works by this author on:
Susan D Arden;
Susan D Arden
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge
Cambridge, United Kingdom
Search for other works by this author on:
John C Hutton;
John C Hutton
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge
Cambridge, United Kingdom
Search for other works by this author on:
G Jan Bruining;
G Jan Bruining
Department of Paediatrics, Sophia Children's Hospital, Erasmus University
Rotterdam, The Netherlands
Search for other works by this author on:
René R P De Vries
René R P De Vries
Department of Immunohaematology and Blood Bank, University Hospital Leiden
Leiden
Search for other works by this author on:
Address correspondence and reprint requests to Dr. Bart 0. Roep, Department of Immunohaematology & Blood Bank, University Hospital Leiden, E3-Q, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Diabetes 1995;44(3):278–283
Article history
Received:
May 02 1994
Revision Received:
November 03 1994
Accepted:
November 03 1994
Citation
Bart O Roep, Aram A Kallan, Gaby Duinkerken, Susan D Arden, John C Hutton, G Jan Bruining, René R P De Vries; T-Cell Reactivity to β-Cell Membrane Antigens Associated With β-Cell Destruction in IDDM. Diabetes 1 March 1995; 44 (3): 278–283. https://doi.org/10.2337/diab.44.3.278
Download citation file:
26
Views