T-cell reactivity to beta-cell membrane antigens associated with beta-cell destruction in IDDM.
Insulin-dependent diabetes mellitus (IDDM) results from a T-cell-mediated destruction of the insulin-producing beta-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 beta-cell antigens with IDDM and the pathogenesis of the disease (the beta-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 beta-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 beta-cell destruction.
Roep
B O
BO
Department of Immunohaematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Kallan
A A
AA
Duinkerken
G
G
Arden
S D
SD
Hutton
J C
JC
Bruining
G J
GJ
de Vries
R R
RR
D000293:Adolescent; D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015925:Cryopreservation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000276:immunology; D007340:Insulinoma / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D010190:Pancreatic Neoplasms / Q000276:immunology; D051381:Rats; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000954:Antigens, Surface; D013745:Tetanus Toxoid